NM_001195263.2:c.2341_2352dupCGCAGCCGCAGC

Variant names:

• chr10-101010536-T-TGCTGCGGCTGCG
• rs200896335
• NM_001195263.2:c.2341_2352dupCGCAGCCGCAGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001195263.2(PDZD7):​c.2341_2352dupCGCAGCCGCAGC​(p.Ser784_Ser785insArgSerArgSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,523,954 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PDZD7 NM_001195263.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001195263.2

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.2341_2352dupCGCAGCCGCAGC	p.Ser784_Ser785insArgSerArgSer	conservative_inframe_insertion	Exon 15 of 17	NP_001182192.1
	PDZD7	NM_001437429.1		c.2338_2349dupCGCAGCCGCAGC	p.Ser783_Ser784insArgSerArgSer	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.2341_2352dupCGCAGCCGCAGC	p.Ser784_Ser785insArgSerArgSer	conservative_inframe_insertion	Exon 15 of 17	ENSP00000480489.1
	PDZD7	ENST00000912190.1		c.2338_2349dupCGCAGCCGCAGC	p.Ser783_Ser784insArgSerArgSer	conservative_inframe_insertion	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2288_*2299dupCGCAGCCGCAGC		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 41 AN: 151384 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.0000957

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.000482

GnomAD2 exomes AF: 0.000210 AC: 27 AN: 128718 AF XY: 0.000244

Gnomad AFR exome AF: 0.000623

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000857

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000806

Gnomad OTH exome AF: 0.000250

GnomAD4 exome AF: 0.000153 AC: 210 AN: 1372456 Hom.: 0 Cov.: 98 AF XY: 0.000157 AC XY: 106 AN XY: 675330

African (AFR) AF: 0.000446 AC: 14 AN: 31396

American (AMR) AF: 0.000283 AC: 10 AN: 35320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24594

East Asian (EAS) AF: 0.000845 AC: 30 AN: 35512

South Asian (SAS) AF: 0.000166 AC: 13 AN: 78340

European-Finnish (FIN) AF: 0.0000596 AC: 2 AN: 33538

Middle Eastern (MID) AF: 0.000358 AC: 2 AN: 5594

European-Non Finnish (NFE) AF: 0.000123 AC: 132 AN: 1070816

Other (OTH) AF: 0.000122 AC: 7 AN: 57346

GnomAD4 genome AF: 0.000264 AC: 40 AN: 151498 Hom.: 0 Cov.: 0 AF XY: 0.000230 AC XY: 17 AN XY: 73966

African (AFR) AF: 0.000580 AC: 24 AN: 41400

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4800

European-Finnish (FIN) AF: 0.0000957 AC: 1 AN: 10446

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

European-Non Finnish (NFE) AF: 0.0000886 AC: 6 AN: 67698

Other (OTH) AF: 0.000477 AC: 1 AN: 2098

Alfa AF: 0.0000546 Hom.: 1561

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

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;