chr6-129216731-T-C

Variant names:

• chr6-129216731-T-C
• rs265360
• NM_000426.4:c.1782+23878T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000426.4(LAMA2):​c.1782+23878T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,060 control chromosomes in the GnomAD database, including 34,532 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (34532 hom., cov: 33)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.1782+23878T>C		intron_variant	Intron 12 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.1782+23878T>C		intron_variant	Intron 12 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.1782+23878T>C		intron_variant	Intron 12 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.1782+23878T>C		intron_variant	Intron 12 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.1782+23878T>C		intron_variant	Intron 12 of 63	5		ENSP00000481744.2
LAMA2	ENST00000690881.1	n.1246-23810T>C		intron_variant	Intron 9 of 9

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98989 AN: 151942 Hom.: 34544 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.675

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.651 AC: 98997 AN: 152060 Hom.: 34532 Cov.: 33 AF XY: 0.654 AC XY: 48613 AN XY: 74328

African (AFR) AF: 0.383 AC: 15870 AN: 41454

American (AMR) AF: 0.751 AC: 11475 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2483 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2652 AN: 5168

South Asian (SAS) AF: 0.710 AC: 3421 AN: 4818

European-Finnish (FIN) AF: 0.756 AC: 7991 AN: 10568

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52823 AN: 67974

Other (OTH) AF: 0.672 AC: 1421 AN: 2114

Alfa AF: 0.743 Hom.: 75871

Bravo AF: 0.634

Asia WGS AF: 0.602 AC: 2092 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.86
PhyloP100		0.81
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: rs265360; hg19: chr6-129537876;