NM_001195263.2:c.2347_2352dupCGCAGC

Variant names:

• chr10-101010536-T-TGCTGCG
• rs200896335
• NM_001195263.2:c.2347_2352dupCGCAGC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.2347_2352dupCGCAGC​(p.Ser784_Ser785insArgSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,523,516 control chromosomes in the GnomAD database, including 154,616 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11806 hom., cov: 0)
  • Exomes 𝑓: 0.45 (142810 hom.)
• Consequence: PDZD7 NM_001195263.2 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.894
• Publications: 10 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: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive 57

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001195263.2
• BP6: Variant 10-101010536-T-TGCTGCG is Benign according to our data. Variant chr10-101010536-T-TGCTGCG is described in ClinVar as Benign. ClinVar VariationId is 44126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	NM_001195263.2	MANE Select	c.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	Exon 15 of 17	NP_001182192.1
	PDZD7	NM_001437429.1		c.2344_2349dupCGCAGC	p.Ser783_Ser784insArgSer	conservative_inframe_insertion	Exon 15 of 17	NP_001424358.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	Exon 15 of 17	ENSP00000480489.1
	PDZD7	ENST00000912190.1		c.2344_2349dupCGCAGC	p.Ser783_Ser784insArgSer	conservative_inframe_insertion	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2294_*2299dupCGCAGC		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54483 AN: 151212 Hom.: 11808 Cov.: 0

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.383 AC: 49335 AN: 128718 AF XY: 0.388

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.485

Gnomad EAS exome AF: 0.0572

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.474

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.446 AC: 612106 AN: 1372190 Hom.: 142810 Cov.: 98 AF XY: 0.445 AC XY: 300439 AN XY: 675136

African (AFR) AF: 0.120 AC: 3756 AN: 31394

American (AMR) AF: 0.369 AC: 13042 AN: 35310

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 12319 AN: 24584

East Asian (EAS) AF: 0.0478 AC: 1698 AN: 35510

South Asian (SAS) AF: 0.373 AC: 29212 AN: 78304

European-Finnish (FIN) AF: 0.481 AC: 16118 AN: 33522

Middle Eastern (MID) AF: 0.418 AC: 2336 AN: 5588

European-Non Finnish (NFE) AF: 0.477 AC: 510369 AN: 1070652

Other (OTH) AF: 0.406 AC: 23256 AN: 57326

GnomAD4 genome AF: 0.360 AC: 54487 AN: 151326 Hom.: 11806 Cov.: 0 AF XY: 0.359 AC XY: 26538 AN XY: 73868

African (AFR) AF: 0.138 AC: 5690 AN: 41342

American (AMR) AF: 0.395 AC: 6013 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1706 AN: 3460

East Asian (EAS) AF: 0.0625 AC: 323 AN: 5168

South Asian (SAS) AF: 0.363 AC: 1735 AN: 4786

European-Finnish (FIN) AF: 0.481 AC: 5015 AN: 10430

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32581 AN: 67636

Other (OTH) AF: 0.366 AC: 767 AN: 2096

Alfa AF: 0.351 Hom.: 1561

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Hearing loss, autosomal recessive 57 (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs200896335; hg19: chr10-102770293; COSMIC: COSV64651345; COSMIC: COSV64651345;