rs1560143

Variant names:

• chr5-31642097-A-G
• rs1560143
• NM_178140.4:c.-361+2660A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.-361+2660A>G		intron_variant	Intron 1 of 24	ENST00000438447.2	NP_835260.2
PDZD2	XM_005248269.5	c.-361+2660A>G		intron_variant	Intron 1 of 25		XP_005248326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.-361+2660A>G		intron_variant	Intron 1 of 24	1	NM_178140.4	ENSP00000402033.1

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

African (AFR) AF: 0.264 AC: 10935 AN: 41458

American (AMR) AF: 0.485 AC: 7402 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3028 AN: 5148

South Asian (SAS) AF: 0.683 AC: 3283 AN: 4806

European-Finnish (FIN) AF: 0.624 AC: 6585 AN: 10558

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43570 AN: 67970

Other (OTH) AF: 0.539 AC: 1131 AN: 2100

Alfa AF: 0.593 Hom.: 84275

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
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1560143; hg19: chr5-31642204;