rs150917752

Variant names:

• chr10-101030064-G-A
• rs150917752
• NM_001195263.2:c.156C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101030064-G-A
• chr10-101030064-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001195263.2(PDZD7):​c.156C>T​(p.Asn52Asn) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.364
• Publications: 2 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=-0.58).
• BP6: Variant 10-101030064-G-A is Benign according to our data. Variant chr10-101030064-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.364 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000798 (121/151648) while in subpopulation EAS AF = 0.00707 (36/5094). AF 95% confidence interval is 0.00525. There are 0 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR,Unknown gene

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.156C>T	p.Asn52Asn	synonymous	Exon 2 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 17	NP_001424358.1
	PDZD7	NM_001351044.2		c.156C>T	p.Asn52Asn	synonymous	Exon 2 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.156C>T	p.Asn52Asn	synonymous	Exon 2 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 17	ENSP00000582249.1
	PDZD7	ENST00000645349.1		c.156C>T	p.Asn52Asn	synonymous	Exon 2 of 10	ENSP00000495283.1	A0A2R8YFN1

Frequencies

GnomAD3 genomes AF: 0.000792 AC: 120 AN: 151520 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00132 AC: 332 AN: 250814 AF XY: 0.00133

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.0000225 AC: 1 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25916

East Asian (EAS) AF: 0.0124 AC: 488 AN: 39380

South Asian (SAS) AF: 0.00119 AC: 103 AN: 86214

European-Finnish (FIN) AF: 0.00611 AC: 323 AN: 52896

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5676

European-Non Finnish (NFE) AF: 0.000168 AC: 186 AN: 1108712

Other (OTH) AF: 0.00125 AC: 75 AN: 60060

GnomAD4 genome AF: 0.000798 AC: 121 AN: 151648 Hom.: 0 Cov.: 33 AF XY: 0.00112 AC XY: 83 AN XY: 74154

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00707 AC: 36 AN: 5094

South Asian (SAS) AF: 0.00126 AC: 6 AN: 4748

European-Finnish (FIN) AF: 0.00496 AC: 52 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000398 AC: 27 AN: 67878

Other (OTH) AF: 0.00 AC: 0 AN: 2108

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.9
DANN	Benign	0.94
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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