rs372962551

Variant names:

• chr6-129312825-TTG-T
• rs372962551
• NM_000426.4:c.3175-32_3175-31delGT

Your query was ambiguous. Multiple possible variants found:

• chr6-129312825-TTG-T
• chr6-129312825-TTG-TTGTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.3175-32_3175-31delGT 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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• congenital merosin-deficient muscular dystrophy 1A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• LAMA2-related muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy, limb-girdle, autosomal recessive 23

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.3175-32_3175-31delGT		intron_variant	Intron 22 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.3175-32_3175-31delGT		intron_variant	Intron 22 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.3175-35_3175-34delTG		intron_variant	Intron 22 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.3439-35_3439-34delTG		intron_variant	Intron 23 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.3175-35_3175-34delTG		intron_variant	Intron 22 of 63	5		ENSP00000481744.2

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

GnomAD2 exomes AF: 0.135 AC: 33557 AN: 247754 AF XY: 0.128

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 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

African (AFR) AF: 0.0785 AC: 2250 AN: 28676

American (AMR) AF: 0.266 AC: 11742 AN: 44132

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 2400 AN: 24538

East Asian (EAS) AF: 0.386 AC: 14881 AN: 38586

South Asian (SAS) AF: 0.0954 AC: 7752 AN: 81218

European-Finnish (FIN) AF: 0.124 AC: 6624 AN: 53244

Middle Eastern (MID) AF: 0.121 AC: 644 AN: 5308

European-Non Finnish (NFE) AF: 0.0814 AC: 72586 AN: 891780

Other (OTH) AF: 0.112 AC: 5854 AN: 52222

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

African (AFR) AF: 0.0778 AC: 3232 AN: 41536

American (AMR) AF: 0.203 AC: 3103 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2013 AN: 5152

South Asian (SAS) AF: 0.103 AC: 499 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10590

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5406 AN: 68012

Other (OTH) AF: 0.111 AC: 234 AN: 2116

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

May 27, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs372962551; hg19: chr6-129633970;