chr5-32000377-T-C

Position:

• chr5-32000377-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.1254+106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,219,698 control chromosomes in the GnomAD database, including 423,177 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 0.70 (41010 hom., cov: 34)
  • Exomes 𝑓: 0.84 (382167 hom.)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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]

PDZD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.1254+106T>C		intron_variant		ENST00000438447.2	NP_835260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.1254+106T>C		intron_variant		1	NM_178140.4	ENSP00000402033.1
PDZD2	ENST00000502489.5	n.1010+106T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106445 AN: 152094 Hom.: 41013 Cov.: 34

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.836 AC: 892560 AN: 1067488 Hom.: 382167 AF XY: 0.837 AC XY: 454384 AN XY: 542858

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.818

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.849

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.797

GnomAD4 genome AF: 0.699 AC: 106458 AN: 152210 Hom.: 41010 Cov.: 34 AF XY: 0.697 AC XY: 51848 AN XY: 74438

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.706

Alfa AF: 0.841 Hom.: 72770

Bravo AF: 0.673

Asia WGS AF: 0.543 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.65

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: rs10054504; hg19: chr5-32000483; COSMIC: COSV56851588;