rs569520095

Positions:

• chr10-101008626-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001195263.2(PDZD7):​c.2943T>C​(p.Asp981=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,535,920 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (11 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.445

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-101008626-A-G is Benign according to our data. Variant chr10-101008626-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 506083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101008626-A-G is described in Lovd as [Benign]. Variant chr10-101008626-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.445 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.2943T>C	p.Asp981=	synonymous_variant	17/17	ENST00000619208.6
PDZD7	XM_011540177.4	c.2943T>C	p.Asp981=	synonymous_variant	18/18
PDZD7	XM_047425767.1	c.2943T>C	p.Asp981=	synonymous_variant	17/17
PDZD7	XM_011540178.4	c.2940T>C	p.Asp980=	synonymous_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.2943T>C	p.Asp981=	synonymous_variant	17/17	5	NM_001195263.2	P1
PDZD7	ENST00000474125.7	c.*2890T>C		3_prime_UTR_variant, NMD_transcript_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152028 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00223 AC: 301 AN: 135044 Hom.: 1 AF XY: 0.00237 AC XY: 174 AN XY: 73424

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.000940

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00462

Gnomad FIN exome AF: 0.00350

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00288

GnomAD4 exome AF: 0.00253 AC: 3501 AN: 1383774 Hom.: 11 Cov.: 33 AF XY: 0.00259 AC XY: 1769 AN XY: 682834

Gnomad4 AFR exome AF: 0.000380

Gnomad4 AMR exome AF: 0.000952

Gnomad4 ASJ exome AF: 0.000715

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00464

Gnomad4 FIN exome AF: 0.00358

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.00189 AC: 287 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.00191 AC XY: 142 AN XY: 74388

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00204 Hom.: 0

Bravo AF: 0.00159

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	PDZD7: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Asp981Asp in exon 17 of PDZD7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.47% (36/7620) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs569520095). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs569520095; hg19: chr10-102768383; COSMIC: COSV64651935; COSMIC: COSV64651935;