10-101010536-T-TGCTGCG

Position:

• chr10-101010536-T-TGCTGCG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.2347_2352dupCGCAGC​(p.Ser784_Ser785insArgSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,523,516 control chromosomes in the GnomAD database, including 154,616 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11806 hom., cov: 0)
  • Exomes 𝑓: 0.45 (142810 hom.)
• Consequence: PDZD7 NM_001195263.2 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.894

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 10-101010536-T-TGCTGCG is Benign according to our data. Variant chr10-101010536-T-TGCTGCG is described in ClinVar as [Benign]. Clinvar id is 44126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	15/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	15/17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2294_*2299dupCGCAGC		non_coding_transcript_exon_variant	11/13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2294_*2299dupCGCAGC		3_prime_UTR_variant	11/13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54483 AN: 151212 Hom.: 11808 Cov.: 0

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.383 AC: 49335 AN: 128718 Hom.: 10799 AF XY: 0.388 AC XY: 27044 AN XY: 69728

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.485

Gnomad EAS exome AF: 0.0572

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.446 AC: 612106 AN: 1372190 Hom.: 142810 Cov.: 98 AF XY: 0.445 AC XY: 300439 AN XY: 675136

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.0478

Gnomad4 SAS exome AF: 0.373

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.360 AC: 54487 AN: 151326 Hom.: 11806 Cov.: 0 AF XY: 0.359 AC XY: 26538 AN XY: 73868

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.366

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 05, 2012	Arg783_Ser784dup in exon 15A of PDZD7: This variant is not expected to have clin ical significance because it has been identified in 27% (584/2178) of chromosome s from a broad population (1000Genomes, dbSNP rs200896335). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 22, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 05, 2015	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 06, 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	- -

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200896335; hg19: chr10-102770293;