6-129391562-G-C

Variant names:

• chr6-129391562-G-C
• rs539321303
• NM_000426.4:c.5143G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000426.4(LAMA2):​c.5143G>C​(p.Glu1715Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: LAMA2 NM_000426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083468825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.5143G>C	p.Glu1715Gln	missense_variant	Exon 36 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.5143G>C	p.Glu1715Gln	missense_variant	Exon 36 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.5143G>C	p.Glu1715Gln	missense_variant	Exon 36 of 65	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.5407G>C	p.Glu1803Gln	missense_variant	Exon 37 of 66	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.5143G>C	p.Glu1715Gln	missense_variant	Exon 36 of 64	5		ENSP00000481744.2
LAMA2	ENST00000687590.1	n.1563G>C		non_coding_transcript_exon_variant	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	15
DANN	Benign	0.66
DEOGEN2	Benign	0.011	.;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.97	.;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.5	.;.;N
REVEL	Benign	0.12
Sift	Benign	1.0	.;.;T
Polyphen		0.0	.;.;B
Vest4		0.072
MutPred		0.42		Gain of MoRF binding (P = 0.0458);Gain of MoRF binding (P = 0.0458);Gain of MoRF binding (P = 0.0458);
MVP		0.34
MPC		0.088
ClinPred		0.12	T
GERP RS		4.3
Varity_R		0.070
gMVP		0.099

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

Other links and lift over

dbSNP: rs539321303; hg19: chr6-129712707;