GeneBe

NM_001195263.2:c.2991C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001195263.2(PDZD7):​c.2991C>A​(p.Pro997Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,535,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

Publications

0 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 10-101008578-G-T is Benign according to our data. Variant chr10-101008578-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2019964.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.34 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDZD7NM_001195263.2 linkc.2991C>A p.Pro997Pro synonymous_variant Exon 17 of 17 ENST00000619208.6 NP_001182192.1 Q9H5P4-3
PDZD7NM_001437429.1 linkc.2988C>A p.Pro996Pro synonymous_variant Exon 17 of 17 NP_001424358.1
PDZD7XM_011540177.4 linkc.2991C>A p.Pro997Pro synonymous_variant Exon 18 of 18 XP_011538479.1 Q9H5P4-3
PDZD7XM_047425767.1 linkc.2991C>A p.Pro997Pro synonymous_variant Exon 17 of 17 XP_047281723.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDZD7ENST00000619208.6 linkc.2991C>A p.Pro997Pro synonymous_variant Exon 17 of 17 5 NM_001195263.2 ENSP00000480489.1 Q9H5P4-3
PDZD7ENST00000474125.7 linkn.*2938C>A non_coding_transcript_exon_variant Exon 13 of 13 2 ENSP00000474447.1 S4R3J9
PDZD7ENST00000474125.7 linkn.*2938C>A 3_prime_UTR_variant Exon 13 of 13 2 ENSP00000474447.1 S4R3J9

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
31
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1383884
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
682860
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31588
American (AMR)
AF:
0.00
AC:
0
AN:
35700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25176
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35734
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79216
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34078
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5612
European-Non Finnish (NFE)
AF:
9.27e-7
AC:
1
AN:
1078878
Other (OTH)
AF:
0.00
AC:
0
AN:
57902
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74240
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41382
American (AMR)
AF:
0.00
AC:
0
AN:
15240
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67984
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 27, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.2
DANN
Benign
0.80
PhyloP100
1.3

Splicing

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

Publications

Other links and lift over

dbSNP: rs1273046835; hg19: chr10-102768335; API