rs3828735

Variant names:

• chr6-129403797-T-A
• rs3828735
• NM_000426.4:c.5727-24T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-129403797-T-A
• chr6-129403797-T-C
• chr6-129403797-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.5727-24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,594,536 control chromosomes in the GnomAD database, including 176,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19480 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157112 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.28
• Publications: 4 publications found

Genes affected

LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

LAMA2 Gene-Disease associations (from GenCC):

• congenital merosin-deficient muscular dystrophy 1A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• LAMA2-related muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy, limb-girdle, autosomal recessive 23

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-129403797-T-A is Benign according to our data. Variant chr6-129403797-T-A is described in ClinVar as Benign. ClinVar VariationId is 256076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.5727-24T>A		intron_variant	Intron 39 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.5727-24T>A		intron_variant	Intron 39 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.5727-24T>A		intron_variant	Intron 39 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.5991-24T>A		intron_variant	Intron 40 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.5727-24T>A		intron_variant	Intron 39 of 63	5		ENSP00000481744.2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75842 AN: 151470 Hom.: 19436 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.493

GnomAD2 exomes AF: 0.485 AC: 121078 AN: 249442 AF XY: 0.485

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.567

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.472

GnomAD4 exome AF: 0.462 AC: 667086 AN: 1442946 Hom.: 157112 Cov.: 32 AF XY: 0.464 AC XY: 333496 AN XY: 718816

African (AFR) AF: 0.630 AC: 20824 AN: 33044

American (AMR) AF: 0.473 AC: 21119 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 13799 AN: 26016

East Asian (EAS) AF: 0.531 AC: 21036 AN: 39590

South Asian (SAS) AF: 0.539 AC: 46311 AN: 85884

European-Finnish (FIN) AF: 0.457 AC: 23972 AN: 52492

Middle Eastern (MID) AF: 0.511 AC: 2935 AN: 5742

European-Non Finnish (NFE) AF: 0.446 AC: 488797 AN: 1095670

Other (OTH) AF: 0.473 AC: 28293 AN: 59818

GnomAD4 genome AF: 0.501 AC: 75955 AN: 151590 Hom.: 19480 Cov.: 32 AF XY: 0.501 AC XY: 37119 AN XY: 74036

African (AFR) AF: 0.616 AC: 25437 AN: 41296

American (AMR) AF: 0.458 AC: 6984 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1772 AN: 3464

East Asian (EAS) AF: 0.547 AC: 2806 AN: 5132

South Asian (SAS) AF: 0.529 AC: 2546 AN: 4812

European-Finnish (FIN) AF: 0.438 AC: 4598 AN: 10502

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30211 AN: 67826

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.395 Hom.: 1773

Bravo AF: 0.509

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Merosin deficient congenital muscular dystrophy Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Muscular dystrophy, limb-girdle, autosomal recessive 23 Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3828735; hg19: chr6-129724942; COSMIC: COSV70353211;