rs952940

Variant names:

• chr5-31921944-G-C
• rs952940
• NM_178140.4:c.477-61211G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178140.4(PDZD2):​c.477-61211G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,238 control chromosomes in the GnomAD database, including 59,567 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 0.88 (59567 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.477-61211G>C		intron_variant	Intron 2 of 24	ENST00000438447.2	NP_835260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.477-61211G>C		intron_variant	Intron 2 of 24	1	NM_178140.4	ENSP00000402033.1
PDZD2	ENST00000502489.5	n.233-61211G>C		intron_variant	Intron 1 of 17	2

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134321 AN: 152120 Hom.: 59508 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.883 AC: 134439 AN: 152238 Hom.: 59567 Cov.: 32 AF XY: 0.885 AC XY: 65889 AN XY: 74442

African (AFR) AF: 0.932 AC: 38701 AN: 41538

American (AMR) AF: 0.899 AC: 13749 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3056 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5094 AN: 5188

South Asian (SAS) AF: 0.941 AC: 4542 AN: 4826

European-Finnish (FIN) AF: 0.836 AC: 8856 AN: 10588

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57544 AN: 68020

Other (OTH) AF: 0.886 AC: 1875 AN: 2116

Alfa AF: 0.856 Hom.: 6957

Bravo AF: 0.891

Asia WGS AF: 0.955 AC: 3321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.53
PhyloP100		0.13
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: rs952940; hg19: chr5-31922050;