rs569520095

Variant names:

• chr10-101008626-A-G
• rs569520095
• NM_001195263.2:c.2943T>C
• PDZD7 p.Asp981Asp

Your query was ambiguous. Multiple possible variants found:

• chr10-101008626-A-G
• chr10-101008626-A-C

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.2943T>C​(p.Asp981Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,535,920 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 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (11 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.445
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-101008626-A-G is Benign according to our data. Variant chr10-101008626-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 506083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.445 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00189 (287/152146) while in subpopulation SAS AF = 0.00332 (16/4822). AF 95% confidence interval is 0.00235. There are 0 homozygotes in GnomAd4. There are 142 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 Unknown,AR 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.2943T>C	p.Asp981Asp	synonymous	Exon 17 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2940T>C	p.Asp980Asp	synonymous	Exon 17 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.2943T>C	p.Asp981Asp	synonymous	Exon 17 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2940T>C	p.Asp980Asp	synonymous	Exon 17 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2890T>C		non_coding_transcript_exon	Exon 13 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152028 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00223 AC: 301 AN: 135044 AF XY: 0.00237

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.000940

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00350

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00288

GnomAD4 exome AF: 0.00253 AC: 3501 AN: 1383774 Hom.: 11 Cov.: 33 AF XY: 0.00259 AC XY: 1769 AN XY: 682834

African (AFR) AF: 0.000380 AC: 12 AN: 31594

American (AMR) AF: 0.000952 AC: 34 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.000715 AC: 18 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00464 AC: 368 AN: 79234

European-Finnish (FIN) AF: 0.00358 AC: 122 AN: 34038

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5696

European-Non Finnish (NFE) AF: 0.00260 AC: 2806 AN: 1078696

Other (OTH) AF: 0.00230 AC: 133 AN: 57902

GnomAD4 genome AF: 0.00189 AC: 287 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.00191 AC XY: 142 AN XY: 74388

African (AFR) AF: 0.000265 AC: 11 AN: 41494

American (AMR) AF: 0.00157 AC: 24 AN: 15292

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4822

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00266 AC: 181 AN: 67976

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00204 Hom.: 0

Bravo AF: 0.00159

Asia WGS AF: 0.00231 AC: 8 AN: 3478

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	-0.82
CADD	Benign	0.54
DANN	Benign	0.78
PhyloP100		-0.45

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs569520095;

hg19: chr10-102768383;

COSMIC: COSV64651935;

COSMIC: COSV64651935;