rs150917752

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001195263.2(PDZD7):​c.156C>T​(p.Asn52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000808 in 1,608,340 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00081 ( 11 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.364
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 10-101030064-G-A is Benign according to our data. Variant chr10-101030064-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101030064-G-A is described in Lovd as [Benign]. Variant chr10-101030064-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.364 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000809 (1178/1456692) while in subpopulation EAS AF= 0.0124 (488/39380). AF 95% confidence interval is 0.0115. There are 11 homozygotes in gnomad4_exome. There are 628 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 11 AR,Digenic gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDZD7NM_001195263.2 linkuse as main transcriptc.156C>T p.Asn52= synonymous_variant 2/17 ENST00000619208.6 NP_001182192.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDZD7ENST00000619208.6 linkuse as main transcriptc.156C>T p.Asn52= synonymous_variant 2/175 NM_001195263.2 ENSP00000480489 P1Q9H5P4-3

Frequencies

GnomAD3 genomes
AF:
0.000792
AC:
120
AN:
151520
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00686
Gnomad SAS
AF:
0.00126
Gnomad FIN
AF:
0.00496
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000398
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00132
AC:
332
AN:
250814
Hom.:
3
AF XY:
0.00133
AC XY:
181
AN XY:
135738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00534
Gnomad SAS exome
AF:
0.00101
Gnomad FIN exome
AF:
0.00528
Gnomad NFE exome
AF:
0.000582
Gnomad OTH exome
AF:
0.00344
GnomAD4 exome
AF:
0.000809
AC:
1178
AN:
1456692
Hom.:
11
Cov.:
35
AF XY:
0.000867
AC XY:
628
AN XY:
724716
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.0000386
Gnomad4 EAS exome
AF:
0.0124
Gnomad4 SAS exome
AF:
0.00119
Gnomad4 FIN exome
AF:
0.00611
Gnomad4 NFE exome
AF:
0.000168
Gnomad4 OTH exome
AF:
0.00125
GnomAD4 genome
AF:
0.000798
AC:
121
AN:
151648
Hom.:
0
Cov.:
33
AF XY:
0.00112
AC XY:
83
AN XY:
74154
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00707
Gnomad4 SAS
AF:
0.00126
Gnomad4 FIN
AF:
0.00496
Gnomad4 NFE
AF:
0.000398
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000549
Hom.:
0
Bravo
AF:
0.000268
Asia WGS
AF:
0.00924
AC:
32
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:5
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2020- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024PDZD7: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 08, 2023- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 30, 2012Asn52Asn in Exon 02 of PDZD7: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3/7020 European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs150917752). -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
9.9
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150917752; hg19: chr10-102789821; COSMIC: COSV56519564; COSMIC: COSV56519564; API