6-129440880-T-G

Variant names:

• chr6-129440880-T-G
• NM_000426.4:c.6150T>G

Variant summary

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

The NM_000426.4(LAMA2):​c.6150T>G​(p.Asp2050Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Synonymous variant affecting the same amino acid position (i.e. D2050D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LAMA2 NM_000426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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]

ENSG00000226149 (HGNC:):

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=0.09379926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.6150T>G	p.Asp2050Glu	missense_variant	Exon 43 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.6150T>G	p.Asp2050Glu	missense_variant	Exon 43 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.6150T>G	p.Asp2050Glu	missense_variant	Exon 43 of 65	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.6414T>G	p.Asp2138Glu	missense_variant	Exon 44 of 66	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.6150T>G	p.Asp2050Glu	missense_variant	Exon 43 of 64	5		ENSP00000481744.2
ENSG00000226149	ENST00000665046.1	n.1348A>C		non_coding_transcript_exon_variant	Exon 10 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727162

Gnomad4 AFR exome AF: 0.0000299

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.8
DANN	Benign	0.89
DEOGEN2	Benign	0.018	.;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.86	.;.;N
REVEL	Benign	0.14
Sift	Benign	0.94	.;.;T
Polyphen		0.93	.;.;P
Vest4		0.12
MutPred		0.50		Gain of ubiquitination at K2049 (P = 0.078);Gain of ubiquitination at K2049 (P = 0.078);Gain of ubiquitination at K2049 (P = 0.078);
MVP		0.43
MPC		0.10
ClinPred		0.44	T
GERP RS		0.41
Varity_R		0.043
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-129762025;