rs6450853

Variant names:

• chr5-31678132-G-A
• rs6450853
• NM_178140.4:c.-361+38695G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-31678132-G-A
• chr5-31678132-G-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.-361+38695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,128 control chromosomes in the GnomAD database, including 23,046 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 (23046 hom., cov: 33)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.-361+38695G>A		intron_variant	Intron 1 of 24	ENST00000438447.2	NP_835260.2
PDZD2	XM_005248269.5	c.-361+38695G>A		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+38695G>A		intron_variant	Intron 1 of 24	1	NM_178140.4	ENSP00000402033.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78482 AN: 152010 Hom.: 23046 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.516 AC: 78479 AN: 152128 Hom.: 23046 Cov.: 33 AF XY: 0.520 AC XY: 38660 AN XY: 74370

African (AFR) AF: 0.215 AC: 8932 AN: 41504

American (AMR) AF: 0.563 AC: 8606 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3597 AN: 5176

South Asian (SAS) AF: 0.499 AC: 2402 AN: 4814

European-Finnish (FIN) AF: 0.699 AC: 7406 AN: 10592

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43927 AN: 67976

Other (OTH) AF: 0.501 AC: 1060 AN: 2114

Alfa AF: 0.599 Hom.: 46486

Bravo AF: 0.494

Asia WGS AF: 0.549 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.62
PhyloP100		-0.73
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: rs6450853; hg19: chr5-31678239;