rs775876911
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002292.4(LAMB2):c.713-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002292.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.713-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000305544.9 | NP_002283.3 | |||
LAMB2 | XM_005265127.5 | c.713-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | XP_005265184.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.713-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002292.4 | ENSP00000307156 | P1 | |||
LAMB2 | ENST00000418109.5 | c.713-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000388325 | P1 | ||||
LAMB2 | ENST00000494831.1 | c.266-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | ENSP00000444751 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000897 AC: 22AN: 245148Hom.: 0 AF XY: 0.0000752 AC XY: 10AN XY: 132904
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460956Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726768
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 06, 2022 | This sequence change falls in intron 6 of the LAMB2 gene. It does not directly change the encoded amino acid sequence of the LAMB2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs775876911, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 539740). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at