rs372962551

chr6-129312825-TTG-Tchr6-129312825-TTG-TTGTG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000426.4(LAMA2):c.3175-32_3175-31del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,371,902 control chromosomes in the GnomAD database, including 10,107 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1235 hom., cov: 31)
  • Exomes 𝑓: 0.10 (8872 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0980

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 6-129312825-TTG-T is Benign according to our data. Variant chr6-129312825-TTG-T is described in ClinVar as [Benign]. Clinvar id is 256066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129312825-TTG-T is described in Lovd as [Benign]. Variant chr6-129312825-TTG-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.3175-32_3175-31del		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2	c.3175-32_3175-31del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.3175-32_3175-31del		intron_variant		5	NM_000426.4
LAMA2	ENST00000617695.5	c.3175-32_3175-31del		intron_variant		5
LAMA2	ENST00000618192.5	c.3439-32_3439-31del		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16165 AN: 152080 Hom.: 1233 Cov.: 31

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.135 AC: 33557 AN: 247754 Hom.: 3431 AF XY: 0.128 AC XY: 17122 AN XY: 134234

Gnomad AFR exome AF: 0.0747

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.0954

Gnomad EAS exome AF: 0.388

Gnomad SAS exome AF: 0.0974

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0776

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.102 AC: 124733 AN: 1219704 Hom.: 8872 AF XY: 0.101 AC XY: 62622 AN XY: 619320

Gnomad4 AFR exome AF: 0.0785

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.0978

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.0954

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.106 AC: 16172 AN: 152198 Hom.: 1235 Cov.: 31 AF XY: 0.112 AC XY: 8301 AN XY: 74400

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0944 Hom.: 153

Bravo AF: 0.116

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 27, 2016	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs372962551; hg19: chr6-129633970;