dbSNP rs746898932: LAMA2:p.Tyr1779Asn (chr6-129393145-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000426.4(LAMA2):c.5335T>A(p.Tyr1779Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LAMA2
NM_000426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.5335T>A	p.Tyr1779Asn	missense_variant	Exon 37 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.5335T>A	p.Tyr1779Asn	missense_variant	Exon 37 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.5335T>A	p.Tyr1779Asn	missense_variant	Exon 37 of 65	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.5599T>A	p.Tyr1867Asn	missense_variant	Exon 38 of 66	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.5335T>A	p.Tyr1779Asn	missense_variant	Exon 37 of 64	5		ENSP00000481744.2	A0A087WYF1
LAMA2	ENST00000687590.1 link	n.1755T>A		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.056

.;T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;.;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

.;.;D

REVEL

Benign

0.053

Sift

Benign

0.044

.;.;D

Polyphen

0.23

.;.;B

Vest4

0.57

MutPred

0.72

Gain of disorder (P = 0.0399);Gain of disorder (P = 0.0399);Gain of disorder (P = 0.0399);

MVP

0.48

MPC

0.15

ClinPred

0.70

GERP RS

1.6

Varity_R

0.15

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over