chr10-101010732-G-A

Variant names:

• chr10-101010732-G-A
• rs77081173
• NM_001195263.2:c.2157C>T

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.2157C>T​(p.Asp719Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,295,638 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 25)
  • Exomes 𝑓: 0.0017 (49 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.860
• Publications: 0 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=-0.39).
• BP6: Variant 10-101010732-G-A is Benign according to our data. Variant chr10-101010732-G-A is described in ClinVar as Benign. ClinVar VariationId is 164939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.86 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 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.2157C>T	p.Asp719Asp	synonymous	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2154C>T	p.Asp718Asp	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.2157C>T	p.Asp719Asp	synonymous	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2154C>T	p.Asp718Asp	synonymous	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2104C>T		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 1977 AN: 141412 Hom.: 47 Cov.: 25

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0166

Gnomad NFE AF: 0.000108

Gnomad OTH AF: 0.00711

GnomAD2 exomes AF: 0.00295 AC: 382 AN: 129398 AF XY: 0.00250

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.00223

GnomAD4 exome AF: 0.00165 AC: 1907 AN: 1154128 Hom.: 49 Cov.: 40 AF XY: 0.00140 AC XY: 799 AN XY: 569220

African (AFR) AF: 0.0595 AC: 1562 AN: 26236

American (AMR) AF: 0.00288 AC: 87 AN: 30184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18028

East Asian (EAS) AF: 0.00 AC: 0 AN: 17442

South Asian (SAS) AF: 0.000144 AC: 11 AN: 76414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17412

Middle Eastern (MID) AF: 0.00278 AC: 13 AN: 4670

European-Non Finnish (NFE) AF: 0.0000435 AC: 40 AN: 919470

Other (OTH) AF: 0.00438 AC: 194 AN: 44272

GnomAD4 genome AF: 0.0140 AC: 1983 AN: 141510 Hom.: 47 Cov.: 25 AF XY: 0.0130 AC XY: 891 AN XY: 68296

African (AFR) AF: 0.0484 AC: 1865 AN: 38556

American (AMR) AF: 0.00660 AC: 93 AN: 14088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3362

East Asian (EAS) AF: 0.00 AC: 0 AN: 4428

South Asian (SAS) AF: 0.00 AC: 0 AN: 4172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8702

Middle Eastern (MID) AF: 0.0144 AC: 4 AN: 278

European-Non Finnish (NFE) AF: 0.000108 AC: 7 AN: 65074

Other (OTH) AF: 0.00704 AC: 14 AN: 1990

Alfa AF: 0.00527 Hom.: 2

Bravo AF: 0.0159

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.49
DANN	Benign	0.78
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs77081173; hg19: chr10-102770489;