10-101015809-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001195263.2(PDZD7):​c.1576C>T​(p.Gln526Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

PDZD7
NM_001195263.2 stop_gained, splice_region

Scores

1
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.794
Variant links:
Genes affected
PDZD7 (HGNC:26257): (PDZ domain containing 7) This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-101015809-G-A is Pathogenic according to our data. Variant chr10-101015809-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 545402.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-101015809-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZD7NM_001195263.2 linkuse as main transcriptc.1576C>T p.Gln526Ter stop_gained, splice_region_variant 11/17 ENST00000619208.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZD7ENST00000619208.6 linkuse as main transcriptc.1576C>T p.Gln526Ter stop_gained, splice_region_variant 11/175 NM_001195263.2 P1Q9H5P4-3
PDZD7ENST00000644782.1 linkuse as main transcriptc.1522+2290C>T intron_variant
PDZD7ENST00000474125.7 linkuse as main transcriptc.*1700+2290C>T intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive 57 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJun 01, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.31
N
Vest4
0.014
GERP RS
1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554834186; hg19: chr10-102775566; API