VCV000134664.37 - ClinVar

NM_003482.4(KMT2D):c.2074C>A (p.Pro692Thr)

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_003482.4(KMT2D):c.2074C>A (p.Pro692Thr)

Variation ID: 134664 Accession: VCV000134664.37

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q13.12 12: 49051609 (GRCh38) [ NCBI UCSC ] 12: 49445392 (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	Jun 9, 2014	Oct 20, 2024	Jun 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003482.4:c.2074C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003473.3:p.Pro692Thr	missense
NC_000012.12:g.49051609G>T
NC_000012.11:g.49445392G>T
NG_027827.1:g.8716C>A
	O14686:p.Pro692Thr

... more HGVS ... less HGVS

Protein change

P692T

Other names

Canonical SPDI

NC_000012.12:49051608:G:T

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.

0.00140 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00348

Exome Aggregation Consortium (ExAC) 0.00418

1000 Genomes Project 30x 0.00109

1000 Genomes Project 0.00140

The Genome Aggregation Database (gnomAD) 0.00295

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00335

Links

ClinGen: CA160489 UniProtKB: O14686#VAR_064370 dbSNP: rs202076833 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.
KMT2D		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	5477	5700

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	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Oct 13, 2015	RCV000121371.18
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Jun 1, 2024	RCV000224720.20
Kabuki syndrome	Benign (1)	criteria provided, single submitter	Jan 25, 2024	RCV000345406.11
Kabuki syndrome 1	Benign (1)	criteria provided, single submitter	Sep 16, 2021	RCV002505063.1
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome Kabuki syndrome 1	Likely benign (1)	criteria provided, single submitter	Jul 25, 2022	RCV003224158.1

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 (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000309612.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Sep 16, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Kabuki syndrome 1 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002795463.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 25, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Kabuki syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001012700.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005213086.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Jun 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: SCV004130823.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: KMT2D: BP4, BS1, BS2 Number of individuals with the variant: 8
Likely benign (Feb 08, 2013)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	not specified (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000193423.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014
Benign (Dec 21, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000281048.1 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016
Benign (Oct 13, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000336276.4 First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KMT2D Number of individuals with the variant: 1 Sex: mixed
Benign (Aug 22, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001869773.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021
Likely benign (Jul 25, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome Kabuki syndrome 1 Affected status: unknown Allele origin: germline	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV003920133.1 First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023	Comment: This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.5% (677/117374) including 3 homozygotes … (more) This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.5% (677/117374) including 3 homozygotes (https://gnomad.broadinstitute.org/variant/12-49445392-G-T?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:134664). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. (less)
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001799218.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 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: SCV001973813.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000085553.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic
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Comment:

This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.5% (677/117374) including 3 homozygotes (https://gnomad.broadinstitute.org/variant/12-49445392-G-T?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:134664). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely 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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KMT2D	-	-	-	-

Text-mined citations for rs202076833 ...

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_003482.4(KMT2D):c.2074C>A (p.Pro692Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs202076833 ...