10-101023921-T-C

Position:

• chr10-101023921-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.367+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,614,028 control chromosomes in the GnomAD database, including 287,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31608 hom., cov: 33)
  • Exomes 𝑓: 0.59 (255779 hom.)
• Consequence: PDZD7 NM_001195263.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002722
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.591

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-101023921-T-C is Benign according to our data. Variant chr10-101023921-T-C is described in ClinVar as [Benign]. Clinvar id is 46211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101023921-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.367+7A>G		splice_region_variant, intron_variant		ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.367+7A>G		splice_region_variant, intron_variant		5	NM_001195263.2	P1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96500 AN: 152082 Hom.: 31573 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.613

GnomAD3 exomes AF: 0.565 AC: 142062 AN: 251388 Hom.: 41234 AF XY: 0.564 AC XY: 76625 AN XY: 135878

Gnomad AFR exome AF: 0.800

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.402

Gnomad SAS exome AF: 0.524

Gnomad FIN exome AF: 0.517

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.589 AC: 860722 AN: 1461828 Hom.: 255779 Cov.: 65 AF XY: 0.587 AC XY: 426665 AN XY: 727214

Gnomad4 AFR exome AF: 0.804

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.635 AC: 96575 AN: 152200 Hom.: 31608 Cov.: 33 AF XY: 0.626 AC XY: 46552 AN XY: 74414

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.610

Alfa AF: 0.611 Hom.: 19868

Bravo AF: 0.648

Asia WGS AF: 0.486 AC: 1693 AN: 3478

EpiCase AF: 0.610

EpiControl AF: 0.612

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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	May 07, 2012	367+7A>G in Intron 03 of PDZD7: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 40.2% (2823/7020) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs6584410). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

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	-0.92
CADD	Benign	0.29
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6584410; hg19: chr10-102783678; COSMIC: COSV64645720;