rs565429072

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000426.4(LAMA2):ā€‹c.5382A>Gā€‹(p.Thr1794=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,614,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…). Synonymous variant affecting the same amino acid position (i.e. T1794T) has been classified as Benign.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000095 ( 1 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.27
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 6-129393192-A-G is Benign according to our data. Variant chr6-129393192-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.27 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LAMA2NM_000426.4 linkuse as main transcriptc.5382A>G p.Thr1794= synonymous_variant 37/65 ENST00000421865.3 NP_000417.3
LAMA2NM_001079823.2 linkuse as main transcriptc.5382A>G p.Thr1794= synonymous_variant 37/64 NP_001073291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LAMA2ENST00000421865.3 linkuse as main transcriptc.5382A>G p.Thr1794= synonymous_variant 37/655 NM_000426.4 ENSP00000400365
LAMA2ENST00000618192.5 linkuse as main transcriptc.5646A>G p.Thr1882= synonymous_variant 38/665 ENSP00000480802 P1
LAMA2ENST00000617695.5 linkuse as main transcriptc.5382A>G p.Thr1794= synonymous_variant 37/645 ENSP00000481744
LAMA2ENST00000687590.1 linkuse as main transcriptn.1802A>G non_coding_transcript_exon_variant 5/5

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000167
AC:
42
AN:
251360
Hom.:
1
AF XY:
0.000228
AC XY:
31
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00124
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000951
AC:
139
AN:
1461782
Hom.:
1
Cov.:
31
AF XY:
0.000131
AC XY:
95
AN XY:
727200
show subpopulations
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:
0.00121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152342
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 09, 2016- -
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 20, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2024LAMA2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.94
DANN
Benign
0.41

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs565429072; hg19: chr6-129714337; API