rs35038258

chr10-101019210-G-Achr10-101019210-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001195263.2(PDZD7):c.936C>T(p.Asn312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,535,674 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (26 hom., cov: 32)
  • Exomes 𝑓: 0.019 (295 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.134

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 10-101019210-G-A is Benign according to our data. Variant chr10-101019210-G-A is described in ClinVar as [Benign]. Clinvar id is 46212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.134 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2204/152374) while in subpopulation NFE AF= 0.0208 (1418/68026). AF 95% confidence interval is 0.0199. There are 26 homozygotes in gnomad4. There are 1084 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.936C>T	p.Asn312=	synonymous_variant	8/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.936C>T	p.Asn312=	synonymous_variant	8/17	5	NM_001195263.2	P1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2205 AN: 152256 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.0141 AC: 1932 AN: 136582 Hom.: 19 AF XY: 0.0137 AC XY: 1015 AN XY: 73886

Gnomad AFR exome AF: 0.00364

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00574

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0191 AC: 26416 AN: 1383300 Hom.: 295 Cov.: 33 AF XY: 0.0186 AC XY: 12689 AN XY: 682616

Gnomad4 AFR exome AF: 0.00342

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00563

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0145 AC: 2204 AN: 152374 Hom.: 26 Cov.: 32 AF XY: 0.0145 AC XY: 1084 AN XY: 74518

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0178 Hom.: 8

Bravo AF: 0.0138

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

Asn312Asn in Exon 08 of PDZD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.7% (107/6262) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs35038258). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	6.7
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs35038258; hg19: chr10-102778967;