dbSNP rs35038258: PDZD7:p.Asn312Asn (chr10-101019210-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.134

Publications

3 publications found

Variant links:

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)

PDZD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0186

AC XY:

12689

AN XY:

682616

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1707

3413

5120

6826

8533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0145

AC:

2204

AN:

152374

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1084

AN XY:

74518

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0236

AC:

251

AN:

10626

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0208

AC:

1418

AN:

68026

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

119

238

358

477

596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

(source)

DANN

Benign

0.90

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over