rs138303386
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000426.4(LAMA2):c.4909G>A(p.Glu1637Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000644 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1637Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.4909G>A | p.Glu1637Lys | missense_variant | 34/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.4909G>A | p.Glu1637Lys | missense_variant | 34/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.4909G>A | p.Glu1637Lys | missense_variant | 34/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.5173G>A | p.Glu1725Lys | missense_variant | 35/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.4909G>A | p.Glu1637Lys | missense_variant | 34/64 | 5 | |||
LAMA2 | ENST00000687590.1 | n.1329G>A | non_coding_transcript_exon_variant | 2/5 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250862Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135560
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727204
GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2022 | Identified in one individual in a cohort of 1040 patients with dilated cardiomyopathy and also present in one of 912 healthy controls (Mazzarotto F et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31983221) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 24, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 27, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2021 | The c.4909G>A (p.E1637K) alteration is located in exon 34 (coding exon 34) of the LAMA2 gene. This alteration results from a G to A substitution at nucleotide position 4909, causing the glutamic acid (E) at amino acid position 1637 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at