rs32793

Positions:

• chr5-32073460-A-G
• chr5-32073460-A-T

Variant summary

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

The NM_178140.4(PDZD2):​c.2726-372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,992 control chromosomes in the GnomAD database, including 10,245 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 0.34 (10245 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.2726-372A>G		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.2726-372A>G		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502489.5	n.2482-372A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52348 AN: 151874 Hom.: 10229 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.345 AC: 52412 AN: 151992 Hom.: 10245 Cov.: 32 AF XY: 0.348 AC XY: 25808 AN XY: 74266

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.307

Alfa AF: 0.264 Hom.: 8593

Bravo AF: 0.353

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs32793; hg19: chr5-32073566;