NM_001197104.2(KMT2A):c.173dup (p.Ala59fs) AND Wiedemann-Steiner syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 28, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000988745.2

Allele description [Variation Report for NM_001197104.2(KMT2A):c.173dup (p.Ala59fs)]

NM_001197104.2(KMT2A):c.173dup (p.Ala59fs)

Gene:

KMT2A:lysine methyltransferase 2A [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_001197104.2(KMT2A):c.173dup (p.Ala59fs)

HGVS:

NC_000011.10:g.118436685dup
NG_027813.1:g.5196dup
NM_001197104.2:c.173dupMANE SELECT
NM_005933.4:c.173dup
NP_001184033.1:p.Ala59fs
NP_005924.2:p.Ala59fs
LRG_613:g.5196dup
NC_000011.9:g.118307393_118307394insC
NC_000011.9:g.118307400dup

Protein change:

A59fs

Links:

dbSNP: rs1555138552

NCBI 1000 Genomes Browser:

rs1555138552

Molecular consequence:

NM_001197104.2:c.173dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005933.4:c.173dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Wiedemann-Steiner syndrome (WDSTS)
Synonyms:: Growth deficiency and mental retardation with facial dysmorphism
Identifiers:: MONDO: MONDO:0011518; MedGen: C1854630; OMIM: 605130

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001138595	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV004013826	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30549396, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001138595

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV004013826

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The progression of Wiedemann-Steiner syndrome in adulthood and two novel variants in the KMT2A gene.

Feldman HR, Dlouhy SR, Lah MD, Payne KK, Weaver DD.

Am J Med Genet A. 2019 Feb;179(2):300-305. doi: 10.1002/ajmg.a.60698. Epub 2018 Dec 14.

PubMed [citation]

PMID:: 30549396

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Mendelics, SCV001138595.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV004013826.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been previously reported as de novo in a similarly affected individual (PMID: 30549396, 30549396). The variant has been reported to be associated with KMT2A related disorder (ClinVar ID: VCV000802795 / PMID: 30549396). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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