rs4333331

Variant names:

• chr5-32028543-C-G
• rs4333331
• NM_178140.4:c.1408-8688C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-32028543-C-G
• chr5-32028543-C-T

Variant summary

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

The NM_178140.4(PDZD2):​c.1408-8688C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,880 control chromosomes in the GnomAD database, including 21,768 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 0.53 (21768 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.1408-8688C>G		intron_variant	Intron 6 of 24	ENST00000438447.2	NP_835260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.1408-8688C>G		intron_variant	Intron 6 of 24	1	NM_178140.4	ENSP00000402033.1
PDZD2	ENST00000502489.5	n.1164-8688C>G		intron_variant	Intron 5 of 17	2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80496 AN: 151762 Hom.: 21766 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.530 AC: 80524 AN: 151880 Hom.: 21768 Cov.: 32 AF XY: 0.527 AC XY: 39147 AN XY: 74214

African (AFR) AF: 0.447 AC: 18520 AN: 41394

American (AMR) AF: 0.523 AC: 7976 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.368 AC: 1902 AN: 5166

South Asian (SAS) AF: 0.611 AC: 2934 AN: 4804

European-Finnish (FIN) AF: 0.543 AC: 5715 AN: 10518

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39731 AN: 67952

Other (OTH) AF: 0.517 AC: 1090 AN: 2110

Alfa AF: 0.547 Hom.: 2776

Bravo AF: 0.524

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.0
DANN	Benign	0.74
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: rs4333331; hg19: chr5-32028649;