10-53866870-G-GA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001384140.1(PCDH15):c.3502-14dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,477,920 control chromosomes in the GnomAD database, including 32,181 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001384140.1 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.3502-14_3502-13insT | intron_variant | Intron 26 of 32 | 1 | NM_033056.4 | ENSP00000322604.6 | |||
PCDH15 | ENST00000644397.2 | c.3502-14_3502-13insT | intron_variant | Intron 26 of 37 | NM_001384140.1 | ENSP00000495195.1 |
Frequencies
GnomAD3 genomes AF: 0.258 AC: 38704AN: 149830Hom.: 6331 Cov.: 22
GnomAD3 exomes AF: 0.262 AC: 60911AN: 232130Hom.: 8545 AF XY: 0.254 AC XY: 32017AN XY: 125860
GnomAD4 exome AF: 0.184 AC: 244905AN: 1327986Hom.: 25849 Cov.: 23 AF XY: 0.188 AC XY: 125428AN XY: 667038
GnomAD4 genome AF: 0.258 AC: 38743AN: 149934Hom.: 6332 Cov.: 22 AF XY: 0.267 AC XY: 19476AN XY: 73050
ClinVar
Submissions by phenotype
not specified Benign:2
The c.3502-14dupT variant is classified as benign because it has been identified in 26.4% of total chromosomes, including 9873 homozygotes, by gnomAD (http://gn omad-beta.broadinstitute.org/) -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:2
Variant summary: The PCDH15 c.3502-14dupT variant involves the duplication of an intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 29147/114904 control chromosomes (3844 homozygotes) at a frequency of 0.2536639, which is approximately 80 times the estimated maximal expected allele frequency of a pathogenic PCDH15 variant (0.0031623), strong evidence that this variant is a benign polymorphism. In addition, one clinical diagnostic laboratory/reputable database has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
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Autosomal recessive nonsyndromic hearing loss 23 Benign:1
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Usher syndrome type 1F Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at