rs1532269

Variant names:

• chr5-32018735-C-G
• rs1532269
• NM_178140.4:c.1407+8253C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178140.4(PDZD2):​c.1407+8253C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,162 control chromosomes in the GnomAD database, including 20,676 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 0.49 (20676 hom., cov: 34)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.1407+8253C>G		intron_variant	Intron 6 of 24	ENST00000438447.2	NP_835260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.1407+8253C>G		intron_variant	Intron 6 of 24	1	NM_178140.4	ENSP00000402033.1
PDZD2	ENST00000502489.5	n.1163+8253C>G		intron_variant	Intron 5 of 17	2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75184 AN: 152044 Hom.: 20671 Cov.: 34

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.494 AC: 75201 AN: 152162 Hom.: 20676 Cov.: 34 AF XY: 0.492 AC XY: 36571 AN XY: 74382

African (AFR) AF: 0.249 AC: 10356 AN: 41536

American (AMR) AF: 0.497 AC: 7599 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2029 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1968 AN: 5168

South Asian (SAS) AF: 0.571 AC: 2751 AN: 4818

European-Finnish (FIN) AF: 0.577 AC: 6101 AN: 10568

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42570 AN: 68004

Other (OTH) AF: 0.509 AC: 1074 AN: 2108

Alfa AF: 0.553 Hom.: 3075

Bravo AF: 0.475

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.70
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1532269; hg19: chr5-32018841;