NM_000426.4(LAMA2):c.7121G>A (p.Ser2374Asn) AND LAMA2-related muscular dystrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 26, 2021
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:: RCV001244493.2

Allele description

NM_000426.4(LAMA2):c.7121G>A (p.Ser2374Asn)

Gene:

LAMA2:laminin subunit alpha 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.33

Genomic location:

Preferred name:

NM_000426.4(LAMA2):c.7121G>A (p.Ser2374Asn)

HGVS:

NC_000006.12:g.129464418G>A
NG_008678.1:g.586278G>A
NM_000426.4:c.7121G>AMANE SELECT
NM_001079823.2:c.7121G>A
NP_000417.3:p.Ser2374Asn
NP_001073291.2:p.Ser2374Asn
LRG_409t1:c.7121G>A
LRG_409:g.586278G>A
NC_000006.11:g.129785563G>A
NC_000006.11:g.129785563G>A
NM_000426.3:c.7121G>A

Protein change:

S2374N

Links:

dbSNP: rs755168390

NCBI 1000 Genomes Browser:

rs755168390

Molecular consequence:

NM_000426.4:c.7121G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079823.2:c.7121G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: LAMA2-related muscular dystrophy (LAMA2-RD)
Synonyms:: Laminin alpha 2-related dystrophy
Identifiers:: MONDO: MONDO:0100228; MedGen: C5679788

Recent activity

Clear Turn Off Turn On

transcription elongation factor DST1 [Saccharomyces cerevisiae S288C]
transcription elongation factor DST1 [Saccharomyces cerevisiae S288C]
gi|6321395|ref|NP_011472.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001417718	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001417718

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001417718.2

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

Description

This sequence change replaces serine with asparagine at codon 2374 of the LAMA2 protein (p.Ser2374Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs755168390, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Nov 4, 2023

ClinVar

Relating variation to medicine