rs34693310

Variant names:

• chr10-101010840-C-T
• rs34693310
• NM_001195263.2:c.2049G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-101010840-C-T
• chr10-101010840-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001195263.2(PDZD7):​c.2049G>A​(p.Pro683Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,534,700 control chromosomes in the GnomAD database, including 1,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (461 hom., cov: 31)
  • Exomes 𝑓: 0.033 (1093 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -6.41
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 10-101010840-C-T is Benign according to our data. Variant chr10-101010840-C-T is described in ClinVar as Benign. ClinVar VariationId is 44120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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.2049G>A	p.Pro683Pro	synonymous	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2046G>A	p.Pro682Pro	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.2049G>A	p.Pro683Pro	synonymous	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2046G>A	p.Pro682Pro	synonymous	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*1996G>A		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9046 AN: 152032 Hom.: 460 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0551

GnomAD2 exomes AF: 0.0360 AC: 4737 AN: 131732 AF XY: 0.0364

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.0000958

Gnomad FIN exome AF: 0.0505

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0335 AC: 46248 AN: 1382550 Hom.: 1093 Cov.: 42 AF XY: 0.0335 AC XY: 22851 AN XY: 682158

African (AFR) AF: 0.143 AC: 4516 AN: 31558

American (AMR) AF: 0.0245 AC: 875 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1295 AN: 25182

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35734

South Asian (SAS) AF: 0.0441 AC: 3496 AN: 79194

European-Finnish (FIN) AF: 0.0471 AC: 1578 AN: 33470

Middle Eastern (MID) AF: 0.0394 AC: 198 AN: 5022

European-Non Finnish (NFE) AF: 0.0298 AC: 32121 AN: 1078884

Other (OTH) AF: 0.0375 AC: 2166 AN: 57810

GnomAD4 genome AF: 0.0596 AC: 9065 AN: 152150 Hom.: 461 Cov.: 31 AF XY: 0.0584 AC XY: 4346 AN XY: 74402

African (AFR) AF: 0.139 AC: 5766 AN: 41448

American (AMR) AF: 0.0313 AC: 479 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0383 AC: 185 AN: 4832

European-Finnish (FIN) AF: 0.0458 AC: 485 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1812 AN: 68016

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0340 Hom.: 260

Bravo AF: 0.0623

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.046
DANN	Benign	0.71
PhyloP100		-6.4

Splicing

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

Other links and lift over

dbSNP: rs34693310; hg19: chr10-102770597;