NM_001195263.2:c.2319T>C

Variant names:

• chr10-101010570-A-G
• rs807022
• NM_001195263.2:c.2319T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001195263.2(PDZD7):​c.2319T>C​(p.Arg773Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,515,998 control chromosomes in the GnomAD database, including 518,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50356 hom., cov: 30)
  • Exomes 𝑓: 0.83 (468101 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.522
• Publications: 13 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: 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)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-101010570-A-G is Benign according to our data. Variant chr10-101010570-A-G is described in ClinVar as Benign. ClinVar VariationId is 44124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.522 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

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.2319T>C	p.Arg773Arg	synonymous	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2316T>C	p.Arg772Arg	synonymous	Exon 15 of 17	NP_001424358.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.2319T>C	p.Arg773Arg	synonymous	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2316T>C	p.Arg772Arg	synonymous	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2266T>C		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123470 AN: 151424 Hom.: 50309 Cov.: 30

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.808

GnomAD2 exomes AF: 0.808 AC: 102589 AN: 127004 AF XY: 0.807

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.825

Gnomad EAS exome AF: 0.684

Gnomad FIN exome AF: 0.846

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.829 AC: 1131112 AN: 1364456 Hom.: 468101 Cov.: 92 AF XY: 0.827 AC XY: 555077 AN XY: 670886

African (AFR) AF: 0.793 AC: 24843 AN: 31312

American (AMR) AF: 0.821 AC: 28804 AN: 35092

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 20236 AN: 24398

East Asian (EAS) AF: 0.655 AC: 23208 AN: 35426

South Asian (SAS) AF: 0.779 AC: 60388 AN: 77484

European-Finnish (FIN) AF: 0.842 AC: 28113 AN: 33372

Middle Eastern (MID) AF: 0.779 AC: 4310 AN: 5530

European-Non Finnish (NFE) AF: 0.841 AC: 895006 AN: 1064810

Other (OTH) AF: 0.810 AC: 46204 AN: 57032

GnomAD4 genome AF: 0.815 AC: 123570 AN: 151542 Hom.: 50356 Cov.: 30 AF XY: 0.813 AC XY: 60233 AN XY: 74086

African (AFR) AF: 0.788 AC: 32619 AN: 41396

American (AMR) AF: 0.823 AC: 12545 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2841 AN: 3462

East Asian (EAS) AF: 0.675 AC: 3464 AN: 5132

South Asian (SAS) AF: 0.782 AC: 3762 AN: 4812

European-Finnish (FIN) AF: 0.843 AC: 8910 AN: 10568

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.839 AC: 56739 AN: 67640

Other (OTH) AF: 0.807 AC: 1690 AN: 2094

Alfa AF: 0.830 Hom.: 29432

Bravo AF: 0.814

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Hearing loss, autosomal recessive 57 (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.4
DANN	Benign	0.60
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs807022; hg19: chr10-102770327; COSMIC: COSV64651420; COSMIC: COSV64651420;