rs112571971

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195263.2(PDZD7):c.1613G>A(p.Gly538Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,549,712 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 54 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.908

Publications

1 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: Unknown Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive 57
Inheritance: AR Classification: STRONG Submitted by: 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003160268).

BP6

Variant 10-101015772-C-T is Benign according to our data. Variant chr10-101015772-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00661 (1006/152264) while in subpopulation NFE AF = 0.00778 (529/68008). AF 95% confidence interval is 0.00723. There are 9 homozygotes in GnomAd4. There are 541 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	NM_001195263.2	MANE Select	c.1613G>A	p.Gly538Glu	missense	Exon 11 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.1610G>A	p.Gly537Glu	missense	Exon 11 of 17	NP_001424358.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.1613G>A	p.Gly538Glu	missense	Exon 11 of 17	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000912190.1		c.1610G>A	p.Gly537Glu	missense	Exon 11 of 17	ENSP00000582249.1
PDZD7	ENST00000644782.1		c.1522+2327G>A		intron	N/A	ENSP00000496747.1	A0A2R8Y892

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

1006

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00778

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00695

AC:

1018

AN:

146564

AF XY:

0.00692

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00216

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0319

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.00755

GnomAD4 exome

AF:

0.00676

AC:

9447

AN:

1397448

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

4535

AN XY:

689254

show subpopulations

African (AFR)

AF:

0.000570

AC:

AN:

31574

American (AMR)

AF:

0.00275

AC:

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

25172

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35738

South Asian (SAS)

AF:

0.000581

AC:

AN:

79194

European-Finnish (FIN)

AF:

0.0309

AC:

1488

AN:

48162

Middle Eastern (MID)

AF:

0.000774

AC:

AN:

5168

European-Non Finnish (NFE)

AF:

0.00692

AC:

7464

AN:

1078864

Other (OTH)

AF:

0.00477

AC:

276

AN:

57888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

563

1126

1688

2251

2814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.00661

AC:

1006

AN:

152264

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

541

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41548

American (AMR)

AF:

0.00562

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0305

AC:

324

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00778

AC:

529

AN:

68008

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

152

203

254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00658

Hom.:

Bravo

AF:

0.00406

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00649

AC:

ExAC

AF:

0.00178

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

PDZD7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.71

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

PhyloP100

0.91

PrimateAI

Benign

0.32

Sift4G

Benign

0.95

Vest4

0.056

MVP

0.043

ClinPred

0.013

GERP RS

3.0

Varity_R

0.059

gMVP

0.39

Splicing

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

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over