rs34705415

Variant names:

• chr10-101019135-G-A
• rs34705415
• NM_001195263.2:c.1011C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101019135-G-A
• chr10-101019135-G-C
• chr10-101019135-G-T

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.1011C>T​(p.Tyr337Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,546,464 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (24 hom., cov: 32)
  • Exomes 𝑓: 0.010 (348 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.537
• Publications: 6 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=-0.8).
• BP6: Variant 10-101019135-G-A is Benign according to our data. Variant chr10-101019135-G-A is described in ClinVar as Benign. ClinVar VariationId is 46206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.537 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0654 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.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 17	NP_001424358.1
	PDZD7	NM_001351044.2		c.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 10	NP_001337973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 17	ENSP00000582249.1
	PDZD7	ENST00000645349.1		c.1011C>T	p.Tyr337Tyr	synonymous	Exon 8 of 10	ENSP00000495283.1	A0A2R8YFN1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1533 AN: 152274 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00651

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.000658

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0241 AC: 3558 AN: 147572 AF XY: 0.0270

Gnomad AFR exome AF: 0.00749

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.0196

Gnomad FIN exome AF: 0.000637

Gnomad NFE exome AF: 0.00647

Gnomad OTH exome AF: 0.0158

GnomAD4 exome AF: 0.0101 AC: 14102 AN: 1394072 Hom.: 348 Cov.: 33 AF XY: 0.0122 AC XY: 8398 AN XY: 689050

African (AFR) AF: 0.00718 AC: 232 AN: 32324

American (AMR) AF: 0.0335 AC: 1234 AN: 36864

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 388 AN: 25198

East Asian (EAS) AF: 0.0127 AC: 467 AN: 36756

South Asian (SAS) AF: 0.0748 AC: 5977 AN: 79952

European-Finnish (FIN) AF: 0.000685 AC: 24 AN: 35042

Middle Eastern (MID) AF: 0.0378 AC: 202 AN: 5338

European-Non Finnish (NFE) AF: 0.00442 AC: 4796 AN: 1084380

Other (OTH) AF: 0.0134 AC: 782 AN: 58218

GnomAD4 genome AF: 0.0101 AC: 1533 AN: 152392 Hom.: 24 Cov.: 32 AF XY: 0.0112 AC XY: 832 AN XY: 74520

African (AFR) AF: 0.00651 AC: 271 AN: 41602

American (AMR) AF: 0.0199 AC: 305 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5184

South Asian (SAS) AF: 0.0717 AC: 346 AN: 4828

European-Finnish (FIN) AF: 0.000658 AC: 7 AN: 10632

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00589 AC: 401 AN: 68042

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00664 Hom.: 5

Bravo AF: 0.0106

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Usher syndrome type 2A;C2931213:Usher syndrome type 2C;C4693893:Hearing loss, autosomal recessive 57 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.94
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34705415; hg19: chr10-102778892;