rs143529486
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_017721.5(CC2D1A):c.1424C>T(p.Ser475Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000286 in 1,611,172 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017721.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00145 AC: 220AN: 152002Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000347 AC: 84AN: 241736Hom.: 0 AF XY: 0.000198 AC XY: 26AN XY: 131546
GnomAD4 exome AF: 0.000162 AC: 237AN: 1459052Hom.: 1 Cov.: 32 AF XY: 0.000141 AC XY: 102AN XY: 725692
GnomAD4 genome AF: 0.00147 AC: 224AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.00147 AC XY: 109AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Inborn genetic diseases Uncertain:1
The p.S475L variant (also known as c.1424C>T), located in coding exon 13 of the CC2D1A gene, results from a C to T substitution at nucleotide position 1424. The serine at codon 475 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Intellectual disability, autosomal recessive 3 Uncertain:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Intellectual disability Uncertain:1
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not specified Benign:1
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CC2D1A-related disorder Benign:1
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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at