rs34693310

Positions:

• chr10-101010840-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195263.2(PDZD7):​c.2049G>A​(p.Pro683=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,534,700 control chromosomes in the GnomAD database, including 1,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (461 hom., cov: 31)
  • Exomes 𝑓: 0.033 (1093 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -6.41

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 10-101010840-C-T is Benign according to our data. Variant chr10-101010840-C-T is described in ClinVar as [Benign]. Clinvar id is 44120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010840-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-6.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2049G>A	p.Pro683=	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.2049G>A	p.Pro683=	synonymous_variant	15/17	5	NM_001195263.2	ENSP00000480489	P1
PDZD7	ENST00000474125.7	c.*1996G>A		3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000474447

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9046 AN: 152032 Hom.: 460 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0551

GnomAD3 exomes AF: 0.0360 AC: 4737 AN: 131732 Hom.: 147 AF XY: 0.0364 AC XY: 2624 AN XY: 72106

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.0000958

Gnomad SAS exome AF: 0.0451

Gnomad FIN exome AF: 0.0505

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0335 AC: 46248 AN: 1382550 Hom.: 1093 Cov.: 42 AF XY: 0.0335 AC XY: 22851 AN XY: 682158

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.0000840

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0298

Gnomad4 OTH exome AF: 0.0375

GnomAD4 genome AF: 0.0596 AC: 9065 AN: 152150 Hom.: 461 Cov.: 31 AF XY: 0.0584 AC XY: 4346 AN XY: 74402

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0439 Hom.: 85

Bravo AF: 0.0623

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 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	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Pro683Pro in Exon 15 of PDZD7: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 12.7% (15/118) of ch romosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/p rojects/SNP; rs34693310). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.046
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34693310; hg19: chr10-102770597;