rs13340334

Positions:

• chr5-31798796-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178140.4(PDZD2):​c.-360-93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 167,430 control chromosomes in the GnomAD database, including 2,388 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 0.15 (2310 hom., cov: 32)
  • Exomes 𝑓: 0.086 (78 hom.)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.-360-93T>C		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.-360-93T>C		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502824.1	n.89-93T>C		intron_variant, non_coding_transcript_variant		1
PDZD2	ENST00000513910.1	c.-360-93T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23179 AN: 152044 Hom.: 2306 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.0856 AC: 1307 AN: 15268 Hom.: 78 AF XY: 0.0859 AC XY: 677 AN XY: 7878

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.0565

Gnomad4 ASJ exome AF: 0.0708

Gnomad4 EAS exome AF: 0.00475

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0944

GnomAD4 genome AF: 0.152 AC: 23196 AN: 152162 Hom.: 2310 Cov.: 32 AF XY: 0.145 AC XY: 10783 AN XY: 74396

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.136

Alfa AF: 0.119 Hom.: 1585

Bravo AF: 0.161

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.039
DANN	Benign	0.55

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: rs13340334; hg19: chr5-31798903;