rs11190790

Positions:

• chr10-101012526-A-C
• chr10-101012526-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.1750-268T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,052 control chromosomes in the GnomAD database, including 20,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.48 (20749 hom., cov: 33)
• Consequence: PDZD7 NM_001195263.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.237

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-101012526-A-C is Benign according to our data. Variant chr10-101012526-A-C is described in ClinVar as [Benign]. Clinvar id is 683852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.1750-268T>G		intron_variant		ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.1750-268T>G		intron_variant		5	NM_001195263.2	P1
PDZD7	ENST00000644782.1	c.1523-268T>G		intron_variant
PDZD7	ENST00000474125.7	c.*1701-268T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73258 AN: 151934 Hom.: 20753 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.482 AC: 73265 AN: 152052 Hom.: 20749 Cov.: 33 AF XY: 0.477 AC XY: 35446 AN XY: 74298

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.507

Alfa AF: 0.602 Hom.: 37579

Bravo AF: 0.462

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11190790; hg19: chr10-102772283;