rs778319385

chr6-129401340-C-Achr6-129401340-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000426.4(LAMA2):c.5562C>A(p.Asp1854Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1854N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAMA2 NM_000426.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001639
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0323776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.5562C>A	p.Asp1854Glu	missense_variant, splice_region_variant	38/65	ENST00000421865.3
LAMA2	NM_001079823.2	c.5562C>A	p.Asp1854Glu	missense_variant, splice_region_variant	38/64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.5562C>A	p.Asp1854Glu	missense_variant, splice_region_variant	38/65	5	NM_000426.4
LAMA2	ENST00000618192.5	c.5826C>A	p.Asp1942Glu	missense_variant, splice_region_variant	39/66	5		P1
LAMA2	ENST00000617695.5	c.5562C>A	p.Asp1854Glu	missense_variant, splice_region_variant	38/64	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1393556 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 697338

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.0010
Dann	Benign	0.76
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
Polyphen		0.0	.;.;B
Vest4		0.051
MutPred		0.39		Gain of disorder (P = 0.1621);Gain of disorder (P = 0.1621);Gain of disorder (P = 0.1621);
MVP		0.24
MPC		0.083
ClinPred		0.055	T
GERP RS		-11
Varity_R		0.027
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.19
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: rs778319385; hg19: chr6-129722485;