10-101010521-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.2368A>G(p.Lys790Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0385 in 1,530,350 control chromosomes in the GnomAD database, including 2,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (756 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1333 hom.)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.91

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 (MetaRNN=0.0016091168).
• BP6: Variant 10-101010521-T-C is Benign according to our data. Variant chr10-101010521-T-C is described in ClinVar as [Benign]. Clinvar id is 44127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010521-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.2368A>G	p.Lys790Glu	missense_variant	15/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.2368A>G	p.Lys790Glu	missense_variant	15/17	5	NM_001195263.2	P1
PDZD7	ENST00000474125.7	c.*2315A>G		3_prime_UTR_variant, NMD_transcript_variant	11/13	2

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10842 AN: 150352 Hom.: 752 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0135

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0649

GnomAD3 exomes AF: 0.0389 AC: 5187 AN: 133472 Hom.: 193 AF XY: 0.0387 AC XY: 2807 AN XY: 72622

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0532

Gnomad EAS exome AF: 0.000476

Gnomad SAS exome AF: 0.0453

Gnomad FIN exome AF: 0.0507

Gnomad NFE exome AF: 0.0288

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0348 AC: 48008 AN: 1379880 Hom.: 1333 Cov.: 91 AF XY: 0.0347 AC XY: 23570 AN XY: 680000

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0513

Gnomad4 EAS exome AF: 0.000141

Gnomad4 SAS exome AF: 0.0444

Gnomad4 FIN exome AF: 0.0468

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0405

GnomAD4 genome AF: 0.0722 AC: 10866 AN: 150470 Hom.: 756 Cov.: 32 AF XY: 0.0706 AC XY: 5179 AN XY: 73392

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0291 Hom.: 84

Bravo AF: 0.0757

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0278 AC: 107

ExAC AF: 0.0319 AC: 718

Asia WGS AF: 0.0260 AC: 93 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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. -

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	Lys790Glu in Exon 15 of PDZD7: This variant is not expected to have clinical sig nificance because it has been identified in 13.6% (16/118) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs1 11287837). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	22
Dann	Benign	0.60
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.70	D
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.65	T
Vest4		0.13
ClinPred		0.11	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111287837; hg19: chr10-102770278; COSMIC: COSV64651043; COSMIC: COSV64651043;