VCV000198891.42 - ClinVar

NM_001378120.1(MBD5):c.236G>A (p.Gly79Glu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001378120.1(MBD5):c.236G>A (p.Gly79Glu)

Variation ID: 198891 Accession: VCV000198891.42

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q23.1 2: 148463758 (GRCh38) [ NCBI UCSC ] 2: 149221327 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 9, 2017	Oct 20, 2024	Apr 11, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001378120.1:c.236G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001365049.1:p.Gly79Glu	missense
NM_018328.5:c.236G>A	NP_060798.2:p.Gly79Glu	missense
NC_000002.12:g.148463758G>A
NC_000002.11:g.149221327G>A
NG_017003.2:g.447748G>A

... more HGVS ... less HGVS

Protein change

G79E

Other names

p.G79E:GGA>GAA

Canonical SPDI

NC_000002.12:148463757:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00040 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00031

1000 Genomes Project 0.00040

Trans-Omics for Precision Medicine (TOPMed) 0.00050

The Genome Aggregation Database (gnomAD), exomes 0.00058

The Genome Aggregation Database (gnomAD) 0.00061

Exome Aggregation Consortium (ExAC) 0.00075

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00077

Links

ClinGen: CA247782 dbSNP: rs34995577 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MBD5		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	1540	1618

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 5, 2024	RCV000188125.21
MBD5 associated neurodevelopmental disorder	no classifications from unflagged records (1)	no classifications from unflagged records	Oct 26, 2023	RCV000455290.11
Intellectual disability, autosomal dominant 1	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Apr 11, 2024	RCV000470089.31
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Mar 1, 2024	RCV000712260.32
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Dec 14, 2021	RCV002314674.9
MBD5-related disorder	Likely benign (1)	no assertion criteria provided	Nov 19, 2021	RCV003907633.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Oct 21, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000247908.2 First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017
Likely benign (Apr 13, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000842706.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018	Publications: PubMed (3) PubMed: 21981781‚ 27222293‚ 23055267
Benign (Oct 02, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000241732.8 First in ClinVar: Aug 07, 2015 Last updated: Jul 24, 2021	Comment: This variant is associated with the following publications: (PMID: 27222293, 21981781, 23055267)
Likely benign (Dec 14, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000847582.5 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Apr 11, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Intellectual disability, autosomal dominant 1 Affected status: unknown Allele origin: maternal	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000782477.2 First in ClinVar: Jul 07, 2018 Last updated: May 01, 2024	Comment: BS1, BS2, BS4
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Intellectual disability, autosomal dominant 1 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001135962.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Likely benign (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Intellectual disability, autosomal dominant 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000557165.9 First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024
Likely Benign (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847439.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Comment: The p.Gly79Glu variant in MBD5 is classified as likely benign because it has been identified in 0.1% (75/68004) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). … (more) The p.Gly79Glu variant in MBD5 is classified as likely benign because it has been identified in 0.1% (75/68004) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). ACMG/AMP Criteria applied: BS1. (less)
Likely benign (Mar 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004042083.11 First in ClinVar: Oct 14, 2023 Last updated: Oct 20, 2024	Comment: MBD5: BS1 Number of individuals with the variant: 5
Likely benign (Nov 19, 2021)	no assertion criteria provided Method: clinical testing	MBD5-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004727682.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Uncertain significance (Jan 16, 2018)	Flagged submission flagged submission (EGL Classification Definitions 2015) Method: clinical testing Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000232763.5 First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MBD5 Number of individuals with the variant: 7 Sex: mixed
Likely pathogenic (Oct 01, 2012)	Flagged submission flagged submission (Submitter's publication) Method: research Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	MBD5 associated neurodevelopmental disorder Affected status: yes Allele origin: de novo	Elsea Laboratory, Baylor College of Medicine Accession: SCV000264475.1 First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017	Publications: PubMed (1) PubMed: 25741868 Number of individuals with the variant: 1
Uncertain significance (May 23, 2017)	Flagged submission flagged submission (ACMG Guidelines, 2015) Method: clinical testing Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	Intellectual disability, autosomal dominant 1 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000611479.1 First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017
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Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND).	Mullegama SV	European journal of human genetics : EJHG	2016	PMID: 27222293
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868
The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1.	Cukier HN	Autism research : official journal of the International Society for Autism Research	2012	PMID: 23055267
Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder.	Talkowski ME	American journal of human genetics	2011	PMID: 21981781
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MBD5	-	-	-	-

Text-mined citations for rs34995577 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_001378120.1(MBD5):c.236G>A (p.Gly79Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34995577 ...