NM_001197104.2(KMT2A):c.173dup (p.Ala59fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 18, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003736952.3

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004551680	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 18, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 30549396, 22795537, 25574841, 25810209, 28120103, 29574747, 31157197, 31337854, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004551680

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 18, 2023)

germline

clinical testing

PubMed (9)
[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	germline	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

De novo mutations in MLL cause Wiedemann-Steiner syndrome.

Jones WD, Dafou D, McEntagart M, Woollard WJ, Elmslie FV, Holder-Espinasse M, Irving M, Saggar AK, Smithson S, Trembath RC, Deshpande C, Simpson MA.

Am J Hum Genet. 2012 Aug 10;91(2):358-64. doi: 10.1016/j.ajhg.2012.06.008. Epub 2012 Jul 12.

PubMed [citation]

PMID:: 22795537
PMCID:: PMC3415539

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004551680.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 802795). This premature translational stop signal has been observed in individual(s) with Wiedemann‚ÄìSteiner syndrome (PMID: 30549396). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala59Glyfs*88) in the KMT2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KMT2A are known to be pathogenic (PMID: 22795537, 25574841, 25810209, 28120103, 29574747, 31157197, 31337854).

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

Last Updated: Sep 29, 2024

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