VCV000093215.42 - ClinVar

NM_000528.4(MAN2B1):c.2865G>C (p.Thr955=)

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.

(11)

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(4); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000528.4(MAN2B1):c.2865G>C (p.Thr955=)

Variation ID: 93215 Accession: VCV000093215.42

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.13 19: 12647291 (GRCh38) [ NCBI UCSC ] 19: 12758105 (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	Aug 5, 2018	Oct 20, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000528.4:c.2865G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000519.2:p.Thr955=	synonymous
NM_001173498.2:c.2862G>C	NP_001166969.1:p.Thr954=	synonymous
NC_000019.10:g.12647291C>G
NC_000019.9:g.12758105C>G
NG_008318.1:g.24487G>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:12647290:C:G

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.

0.00240 (G)

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

The Genome Aggregation Database (gnomAD) 0.00175

1000 Genomes Project 30x 0.00203

1000 Genomes Project 0.00240

Trans-Omics for Precision Medicine (TOPMed) 0.00260

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00261

Links

ClinGen: CA221085 dbSNP: rs148108322 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.
MAN2B1		-	-	GRCh38 GRCh37	1562	1738

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 provided	Conflicting interpretations of pathogenicity (5)	criteria provided, conflicting classifications	Sep 1, 2023	RCV000675472.28
Deficiency of alpha-mannosidase	Benign (4)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV001079772.17
not specified	Benign (2)	criteria provided, single submitter	Dec 10, 2021	RCV001705728.4

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.
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Deficiency of alpha-mannosidase Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001121589.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Uncertain significance (May 02, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000110947.8 First in ClinVar: Jan 17, 2014 Last updated: Aug 05, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MAN2B1 Number of individuals with the variant: 1 Sex: mixed
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Deficiency of alpha-mannosidase Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001284284.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (1) PubMed: 22161967 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Benign (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of alpha-mannosidase Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001737260.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Sex: mixed
Benign (Dec 10, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002050904.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Likely benign (Sep 01, 2023)	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: SCV002546067.16 First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024	Comment: MAN2B1: BP4, BP7, BS2 Number of individuals with the variant: 7
Likely benign (Apr 12, 2017)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801161.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001918279.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001927598.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Dec 30, 2019)	no assertion criteria provided Method: clinical testing	Alpha-mannosidosis Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001453906.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001976086.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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
Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.	Riise Stensland HM	Human mutation	2012	PMID: 22161967
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MAN2B1	-	-	-	-

Text-mined citations for rs148108322 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000528.4(MAN2B1):c.2865G>C (p.Thr955=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs148108322 ...