rs77500937
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002292.4(LAMB2):c.1193C>T(p.Thr398Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,238 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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.1193C>T | p.Thr398Ile | missense_variant | 9/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.1193C>T | p.Thr398Ile | missense_variant | 10/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.1193C>T | p.Thr398Ile | missense_variant | 9/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.1193C>T | p.Thr398Ile | missense_variant | 10/33 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00717 AC: 1092AN: 152248Hom.: 18 Cov.: 33
GnomAD3 exomes AF: 0.00188 AC: 472AN: 251312Hom.: 9 AF XY: 0.00124 AC XY: 168AN XY: 135878
GnomAD4 exome AF: 0.000730 AC: 1067AN: 1461872Hom.: 11 Cov.: 33 AF XY: 0.000604 AC XY: 439AN XY: 727242
GnomAD4 genome ? AF: 0.00719 AC: 1095AN: 152366Hom.: 18 Cov.: 33 AF XY: 0.00707 AC XY: 527AN XY: 74512
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2020 | This variant is associated with the following publications: (PMID: 20556798, 30013592) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 07, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kidney disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 13, 2017 | - - |
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
LAMB2-related infantile-onset nephrotic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Pierson syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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