rs1560143

Positions:

• chr5-31642097-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178140.4(PDZD2):​c.-361+2660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,976 control chromosomes in the GnomAD database, including 22,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22612 hom., cov: 31)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

Genes affected

PDZD2 (HGNC:18486): (PDZ domain containing 2) The protein encoded by this gene contains six PDZ domains and shares sequence similarity with pro-interleukin-16 (pro-IL-16). Like pro-IL-16, the encoded protein localizes to the endoplasmic reticulum and is thought to be cleaved by a caspase to produce a secreted peptide containing two PDZ domains. In addition, this gene is upregulated in primary prostate tumors and may be involved in the early stages of prostate tumorigenesis. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.-361+2660A>G		intron_variant		ENST00000438447.2
PDZD2	XM_005248269.5	c.-361+2660A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.-361+2660A>G		intron_variant		1	NM_178140.4	P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78779 AN: 151858 Hom.: 22617 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.518 AC: 78780 AN: 151976 Hom.: 22612 Cov.: 31 AF XY: 0.521 AC XY: 38666 AN XY: 74274

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.539

Alfa AF: 0.611 Hom.: 38907

Bravo AF: 0.491

Asia WGS AF: 0.608 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1560143; hg19: chr5-31642204;