rs200747448
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBS1BS2
The NM_002292.4(LAMB2):c.5026G>A(p.Gly1676Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,613,744 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1676I) has been classified as Likely benign.
Frequency
Consequence
NM_002292.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.5026G>A | p.Gly1676Arg | missense_variant | 30/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.5026G>A | p.Gly1676Arg | missense_variant | 31/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.5026G>A | p.Gly1676Arg | missense_variant | 30/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.5026G>A | p.Gly1676Arg | missense_variant | 31/33 | 1 | P1 | ||
LAMB2 | ENST00000467506.5 | n.136G>A | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
LAMB2 | ENST00000498377.1 | n.681G>A | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152154Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00145 AC: 364AN: 251150Hom.: 6 AF XY: 0.00186 AC XY: 253AN XY: 135778
GnomAD4 exome AF: 0.000741 AC: 1083AN: 1461472Hom.: 13 Cov.: 33 AF XY: 0.00100 AC XY: 728AN XY: 727062
GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152272Hom.: 1 Cov.: 33 AF XY: 0.000631 AC XY: 47AN XY: 74478
ClinVar
Submissions by phenotype
LAMB2-related infantile-onset nephrotic syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare | Apr 30, 2019 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 31, 2017 | - - |
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Pierson syndrome Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at