NM_001195263.2:c.2319_2336delTAGCCGCAGCCGTAGCCG

Variant names:

• chr10-101010552-GCGGCTACGGCTGCGGCTA-G
• rs397516634
• NM_001195263.2:c.2319_2336delTAGCCGCAGCCGTAGCCG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001195263.2(PDZD7):​c.2319_2336delTAGCCGCAGCCGTAGCCG​(p.Ser774_Arg779del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 1,524,830 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. RSRSR773R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 28)
  • Exomes 𝑓: 0.010 (115 hom.)
• Consequence: PDZD7 NM_001195263.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.36

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 -16 ACMG points.

• BP6: Variant 10-101010552-GCGGCTACGGCTGCGGCTA-G is Benign according to our data. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in ClinVar as [Likely_benign]. Clinvar id is 44125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in Lovd as [Likely_benign]. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in Lovd as [Likely_pathogenic].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00673 (1021/151680) while in subpopulation NFE AF= 0.011 (746/67720). AF 95% confidence interval is 0.0104. There are 5 homozygotes in gnomad4. There are 477 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	Exon 15 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2266_*2283delTAGCCGCAGCCGTAGCCG		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2266_*2283delTAGCCGCAGCCGTAGCCG		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes AF: 0.00674 AC: 1021 AN: 151560 Hom.: 5 Cov.: 28

Gnomad AFR AF: 0.00201

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00807

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00418

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00866

GnomAD3 exomes AF: 0.00624 AC: 818 AN: 130986 Hom.: 9 AF XY: 0.00621 AC XY: 442 AN XY: 71130

Gnomad AFR exome AF: 0.000779

Gnomad AMR exome AF: 0.00404

Gnomad ASJ exome AF: 0.00521

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00325

Gnomad FIN exome AF: 0.00118

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.00863

GnomAD4 exome AF: 0.0103 AC: 14150 AN: 1373150 Hom.: 115 AF XY: 0.0101 AC XY: 6813 AN XY: 676036

Gnomad4 AFR exome AF: 0.00166

Gnomad4 AMR exome AF: 0.00446

Gnomad4 ASJ exome AF: 0.00567

Gnomad4 EAS exome AF: 0.000169

Gnomad4 SAS exome AF: 0.00393

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.00943

GnomAD4 genome AF: 0.00673 AC: 1021 AN: 151680 Hom.: 5 Cov.: 28 AF XY: 0.00643 AC XY: 477 AN XY: 74142

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00806

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00418

Gnomad4 FIN AF: 0.000757

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.00857

Alfa AF: 0.00527 Hom.: 0

Bravo AF: 0.00709

Asia WGS AF: 0.00116 AC: 4 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PDZD7: BS1, BS2 -

Nov 26, 2018

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27068579) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Mar 09, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The Arg779_Ser784del variant in PDZD7 has not been reported in the literature no r previously identified by our laboratory.The frequency of this variant in large European American and African American populations sequenced by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/) was not reported becaus e coverage at this position was insufficient or unavailable. This in-frame delet ion lies in a variable Arg-Ser repeat region that is not conserved in species in cluding other primates. Furthermore, there is inconclusive evidence as to the ro le of the PDZD7 gene in hearing loss with only one case report suggesting PDZD7 could cause nonsyndromic hearing loss based upon a patient with a homozygous tra nslocation that disrupts the long alternate isoform of PDZD7 (Schneider 2009). I n summary, this variant is likely benign based on its presence in a variable rep eat region, lack of conservation across species, and limited evidence supporting a role of PDZD7 in hearing loss. -

Feb 20, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PDZD7-related disorder Benign:1

Nov 30, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397516634; hg19: chr10-102770309;