rs111287837

Variant names:

• chr10-101010521-T-A
• rs111287837
• NM_001195263.2:c.2368A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101010521-T-A
• chr10-101010521-T-C

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001195263.2(PDZD7):​c.2368A>T​(p.Lys790*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000725 in 1,379,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PDZD7 NM_001195263.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 5 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2368A>T	p.Lys790*	stop_gained	Exon 15 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2368A>T	p.Lys790*	stop_gained	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2315A>T		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2315A>T		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379904 Hom.: 0 Cov.: 91 AF XY: 0.00000147 AC XY: 1 AN XY: 680016

African (AFR) AF: 0.0000317 AC: 1 AN: 31502

American (AMR) AF: 0.00 AC: 0 AN: 35578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25106

East Asian (EAS) AF: 0.00 AC: 0 AN: 35580

South Asian (SAS) AF: 0.00 AC: 0 AN: 79136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075818

Other (OTH) AF: 0.00 AC: 0 AN: 57682

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	41
DANN	Benign	0.73
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		3.9
Vest4		0.20
GERP RS		5.5

Splicing

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

Other links and lift over

dbSNP: rs111287837; hg19: chr10-102770278;