rs807022

Positions:

• chr10-101010570-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001195263.2(PDZD7):​c.2319T>C​(p.Arg773=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,515,998 control chromosomes in the GnomAD database, including 518,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50356 hom., cov: 30)
  • Exomes 𝑓: 0.83 (468101 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.522

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-101010570-A-G is Benign according to our data. Variant chr10-101010570-A-G is described in ClinVar as [Benign]. Clinvar id is 44124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010570-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.522 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2319T>C	p.Arg773=	synonymous_variant	15/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2319T>C	p.Arg773=	synonymous_variant	15/17	5	NM_001195263.2	ENSP00000480489	P1
PDZD7	ENST00000474125.7	c.*2266T>C		3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000474447

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123470 AN: 151424 Hom.: 50309 Cov.: 30

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.808

GnomAD3 exomes AF: 0.808 AC: 102589 AN: 127004 Hom.: 41568 AF XY: 0.807 AC XY: 55472 AN XY: 68772

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.825

Gnomad EAS exome AF: 0.684

Gnomad SAS exome AF: 0.776

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.829 AC: 1131112 AN: 1364456 Hom.: 468101 Cov.: 92 AF XY: 0.827 AC XY: 555077 AN XY: 670886

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.829

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.841

Gnomad4 OTH exome AF: 0.810

GnomAD4 genome AF: 0.815 AC: 123570 AN: 151542 Hom.: 50356 Cov.: 30 AF XY: 0.813 AC XY: 60233 AN XY: 74086

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.807

Alfa AF: 0.835 Hom.: 16983

Bravo AF: 0.814

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Arg773Arg in Exon 15 of PDZD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 26.3% (31/118) of chr omosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/pr ojects/SNP; rs807022). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 2C Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Hearing loss, autosomal recessive 57 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.4
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs807022; hg19: chr10-102770327; COSMIC: COSV64651420; COSMIC: COSV64651420;