Variant rs748257607 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000426.4(LAMA2):c.3977G>A(p.Arg1326Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000373 in 1,610,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LAMA2
NM_000426.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.45

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 6-129316090-G-A is Benign according to our data. Variant chr6-129316090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 477466.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.3977G>A	p.Arg1326Gln	missense_variant	27/65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.3977G>A	p.Arg1326Gln	missense_variant	27/64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LAMA2	ENST00000421865.3 linkuse as main transcript	c.3977G>A	p.Arg1326Gln	missense_variant	27/65	5	NM_000426.4	ENSP00000400365
LAMA2	ENST00000618192.5 linkuse as main transcript	c.4241G>A	p.Arg1414Gln	missense_variant	28/66	5		ENSP00000480802	P1
LAMA2	ENST00000617695.5 linkuse as main transcript	c.3977G>A	p.Arg1326Gln	missense_variant	27/64	5		ENSP00000481744

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251230

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1458054

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

725634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LAMA2-related muscular dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.6

.;.;H

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

.;.;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0080

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.45

MutPred

0.79

Loss of phosphorylation at T1323 (P = 0.1045);Loss of phosphorylation at T1323 (P = 0.1045);Loss of phosphorylation at T1323 (P = 0.1045);

MVP

0.70

MPC

0.23

ClinPred

0.97

GERP RS

4.5

Varity_R

0.91

gMVP

0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over