rs727503369

Positions:

• chr10-101010540-GCGGCTGCGGCTGCGGCTA-G
• chr10-101010540-GCGGCTGCGGCTGCGGCTA-GCGGCTGCGGCTGCGGCTACGGCTGCGGCTGCGGCTA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_001195263.2(PDZD7):​c.2331_2348del​(p.Arg779_Ser784del) variant causes a inframe deletion 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R777R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZD7 NM_001195263.2 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.928

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-101010540-GCGGCTGCGGCTGCGGCTA-G is Benign according to our data. Variant chr10-101010540-GCGGCTGCGGCTGCGGCTA-G is described in ClinVar as [Likely_benign]. Clinvar id is 164938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.2331_2348del	p.Arg779_Ser784del	inframe_deletion	15/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.2331_2348del	p.Arg779_Ser784del	inframe_deletion	15/17	5	NM_001195263.2	P1
PDZD7	ENST00000474125.7	c.*2278_*2295del		3_prime_UTR_variant, NMD_transcript_variant	11/13	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 28, 2013

The Arg779_Ser784del variant in PDZD7 has not been reported in the literature. T he frequency of this variant in large European American and African American pop ulations sequenced by the NHLBI Exome Sequencing Project (http://evs.gs.washingt on.edu/EVS/) was not reported because coverage at this position was insufficient or unavailable. This in-frame deletion lies in a variable Arg-Ser repeat region that is not conserved in species including other primates. Furthermore, there i s inconclusive evidence as to the role of the PDZD7 gene in hearing loss with on ly one case report suggesting PDZD7 could cause nonsyndromic hearing loss based upon a patient with a homozygous translocation that disrupts the long alternate isoform of PDZD7 (Schneider 2009). In summary, this variant is likely benign bas ed on its presence in a variable repeat region and lack of conservation across s pecies. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2019

This variant is associated with the following publications: (PMID: 27068579) -

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;