10-101010540-GCGGCTGCGGCTGCGGCTA-GCGGCTGCGGCTGCGGCTACGGCTGCGGCTGCGGCTA

Position:

• chr10-101010540-GCGGCTGCGGCTGCGGCTA-GCGGCTGCGGCTGCGGCTACGGCTGCGGCTGCGGCTA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001195263.2(PDZD7):​c.2331_2348dupTAGCCGCAGCCGCAGCCG​(p.Arg783_Ser784insSerArgSerArgSerArg) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZD7 NM_001195263.2 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2331_2348dupTAGCCGCAGCCGCAGCCG	p.Arg783_Ser784insSerArgSerArgSerArg	disruptive_inframe_insertion	15/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2331_2348dupTAGCCGCAGCCGCAGCCG	p.Arg783_Ser784insSerArgSerArgSerArg	disruptive_inframe_insertion	15/17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2278_*2295dupTAGCCGCAGCCGCAGCCG		non_coding_transcript_exon_variant	11/13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2278_*2295dupTAGCCGCAGCCGCAGCCG		3_prime_UTR_variant	11/13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 99

GnomAD4 genome Cov.: 32

Alfa AF: 0.000253 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 22, 2022

This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 843744). This variant has not been reported in the literature in individuals affected with PDZD7-related conditions. This variant, c.2331_2348dup, results in the insertion of 6 amino acid(s) of the PDZD7 protein (p.Arg779_Ser784dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs727503369; hg19: chr10-102770297;