rs4867084

chr5-31818841-G-Achr5-31818841-G-Cchr5-31818841-G-T

Variant summary

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

The NM_178140.4(PDZD2):c.476+19117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,994 control chromosomes in the GnomAD database, including 12,392 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 0.39 (12392 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.476+19117G>A		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.476+19117G>A		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502824.1	n.924+19117G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59552 AN: 151876 Hom.: 12399 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.392 AC: 59562 AN: 151994 Hom.: 12392 Cov.: 32 AF XY: 0.388 AC XY: 28839 AN XY: 74286

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.413

Alfa AF: 0.459 Hom.: 22686

Bravo AF: 0.389

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.0
Dann	Benign	0.80

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: rs4867084; hg19: chr5-31818948;