rs4333331

chr5-32028543-C-Gchr5-32028543-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	UniProt
PDZD2	NM_178140.4	c.1408-8688C>G		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.1408-8688C>G		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502489.5	n.1164-8688C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.517

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

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: rs4333331; hg19: chr5-32028649;