rs1966983

chr5-31745772-C-A

Variant summary

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

The NM_178140.4(PDZD2):c.-360-53117C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 149,772 control chromosomes in the GnomAD database, including 6,834 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 0.29 (6834 hom., cov: 31)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.-360-53117C>A		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.-360-53117C>A		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502824.1	n.88+52798C>A		intron_variant, non_coding_transcript_variant		1
PDZD2	ENST00000513910.1	c.-443+33681C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44147 AN: 149688 Hom.: 6829 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.295 AC: 44167 AN: 149772 Hom.: 6834 Cov.: 31 AF XY: 0.298 AC XY: 21708 AN XY: 72942

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.278

Alfa AF: 0.290 Hom.: 3695

Bravo AF: 0.298

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.20
Dann	Benign	0.27

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: rs1966983; hg19: chr5-31745879;