rs12186418

chr5-31898484-T-Cchr5-31898484-T-G

Variant summary

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

The NM_178140.4(PDZD2):c.477-84671T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,094 control chromosomes in the GnomAD database, including 26,339 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 0.56 (26339 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.477-84671T>C		intron_variant		ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.477-84671T>C		intron_variant		1	NM_178140.4	P1
PDZD2	ENST00000502489.5	n.232+43316T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84999 AN: 151976 Hom.: 26334 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.559 AC: 85018 AN: 152094 Hom.: 26339 Cov.: 32 AF XY: 0.555 AC XY: 41299 AN XY: 74370

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.587

Alfa AF: 0.587 Hom.: 8636

Bravo AF: 0.533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.78

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: rs12186418; hg19: chr5-31898590;