NM_001195263.2:c.936C>T

Variant names:

• chr10-101019210-G-A
• rs35038258
• NM_001195263.2:c.936C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001195263.2(PDZD7):​c.936C>T​(p.Asn312Asn) 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:6
• Conservation: PhyloP100: 0.134
• Publications: 3 publications found

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]

PDZD7 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive 57

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Usher syndrome type 2C

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195263.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	NM_001195263.2	MANE Select	c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 17	NP_001182192.1
	PDZD7	NM_001437429.1		c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 17	NP_001424358.1
	PDZD7	NM_001351044.2		c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 10	NP_001337973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 17	ENSP00000480489.1
	PDZD7	ENST00000645349.1		c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 10	ENSP00000495283.1
	PDZD7	ENST00000644782.1		c.936C>T	p.Asn312Asn	synonymous	Exon 8 of 12	ENSP00000496747.1

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

GnomAD2 exomes AF: 0.0141 AC: 1932 AN: 136582 AF XY: 0.0137

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 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

African (AFR) AF: 0.00342 AC: 108 AN: 31592

American (AMR) AF: 0.0137 AC: 488 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 363 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35748

South Asian (SAS) AF: 0.00563 AC: 446 AN: 79192

European-Finnish (FIN) AF: 0.0203 AC: 688 AN: 33950

Middle Eastern (MID) AF: 0.0216 AC: 116 AN: 5364

European-Non Finnish (NFE) AF: 0.0215 AC: 23186 AN: 1078740

Other (OTH) AF: 0.0176 AC: 1021 AN: 57852

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

African (AFR) AF: 0.00349 AC: 145 AN: 41600

American (AMR) AF: 0.0168 AC: 258 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.0236 AC: 251 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1418 AN: 68026

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0182 Hom.: 10

Bravo AF: 0.0138

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 06, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 12, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.7
DANN	Benign	0.90
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35038258; hg19: chr10-102778967;