rs148246465
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002292.4(LAMB2):c.3875A>T(p.Asn1292Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000263 in 1,614,200 control chromosomes in the GnomAD database, including 3 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. N1292S) has been classified as Uncertain significance.
Frequency
Consequence
NM_002292.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.3875A>T | p.Asn1292Ile | missense_variant | 25/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.3875A>T | p.Asn1292Ile | missense_variant | 26/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.3875A>T | p.Asn1292Ile | missense_variant | 25/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.3875A>T | p.Asn1292Ile | missense_variant | 26/33 | 1 | P1 | ||
LAMB2 | ENST00000469665.1 | n.105A>T | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
LAMB2 | ENST00000477225.1 | n.306A>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 217AN: 152226Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.000294 AC: 74AN: 251486Hom.: 1 AF XY: 0.000221 AC XY: 30AN XY: 135916
GnomAD4 exome AF: 0.000141 AC: 206AN: 1461856Hom.: 0 Cov.: 34 AF XY: 0.000124 AC XY: 90AN XY: 727236
GnomAD4 genome AF: 0.00144 AC: 219AN: 152344Hom.: 3 Cov.: 33 AF XY: 0.00146 AC XY: 109AN XY: 74500
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
LAMB2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 21, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
LAMB2-related infantile-onset nephrotic syndrome Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Pierson syndrome Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at