rs1554834186

Positions:

• chr10-101015809-G-A
• chr10-101015809-G-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.794

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]

ACMG classification

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	Protein	UniProt
PDZD7	NM_001195263.2	c.1576C>T	p.Gln526Ter	stop_gained, splice_region_variant	11/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.1576C>T	p.Gln526Ter	stop_gained, splice_region_variant	11/17	5	NM_001195263.2	ENSP00000480489	P1
PDZD7	ENST00000644782.1	c.1522+2290C>T		intron_variant				ENSP00000496747
PDZD7	ENST00000474125.7	c.*1700+2290C>T		intron_variant, NMD_transcript_variant		2		ENSP00000474447

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

Submissions by phenotype

Hearing loss, autosomal recessive 57 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 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

Other links and lift over

dbSNP: rs1554834186; hg19: chr10-102775566;