rs34705415

Positions:

• chr10-101019135-G-A
• chr10-101019135-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195263.2(PDZD7):​c.1011C>T​(p.Tyr337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,546,464 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (24 hom., cov: 32)
  • Exomes 𝑓: 0.010 (348 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.537

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=-0.8).
• BP6: Variant 10-101019135-G-A is Benign according to our data. Variant chr10-101019135-G-A is described in ClinVar as [Benign]. Clinvar id is 46206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101019135-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.537 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.1011C>T	p.Tyr337=	synonymous_variant	8/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.1011C>T	p.Tyr337=	synonymous_variant	8/17	5	NM_001195263.2	ENSP00000480489	P1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1533 AN: 152274 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00651

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.000658

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0241 AC: 3558 AN: 147572 Hom.: 125 AF XY: 0.0270 AC XY: 2175 AN XY: 80592

Gnomad AFR exome AF: 0.00749

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.0196

Gnomad SAS exome AF: 0.0752

Gnomad FIN exome AF: 0.000637

Gnomad NFE exome AF: 0.00647

Gnomad OTH exome AF: 0.0158

GnomAD4 exome AF: 0.0101 AC: 14102 AN: 1394072 Hom.: 348 Cov.: 33 AF XY: 0.0122 AC XY: 8398 AN XY: 689050

Gnomad4 AFR exome AF: 0.00718

Gnomad4 AMR exome AF: 0.0335

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.0127

Gnomad4 SAS exome AF: 0.0748

Gnomad4 FIN exome AF: 0.000685

Gnomad4 NFE exome AF: 0.00442

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0101 AC: 1533 AN: 152392 Hom.: 24 Cov.: 32 AF XY: 0.0112 AC XY: 832 AN XY: 74520

Gnomad4 AFR AF: 0.00651

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.000658

Gnomad4 NFE AF: 0.00589

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00664 Hom.: 5

Bravo AF: 0.0106

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Tyr337Tyr 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 0.8% (53/6688) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34705415). -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 23, 2020	- -

Usher syndrome type 2A;C2931213:Usher syndrome type 2C;C4693893:Hearing loss, autosomal recessive 57 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.94

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: rs34705415; hg19: chr10-102778892;