5-31678091-A-G

Variant names:

• chr5-31678091-A-G
• rs4867365
• NM_178140.4:c.-361+38654A>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.-361+38654A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,192 control chromosomes in the GnomAD database, including 3,769 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 0.22 (3769 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.-361+38654A>G		intron_variant	Intron 1 of 24	ENST00000438447.2	NP_835260.2
PDZD2	XM_005248269.5	c.-361+38654A>G		intron_variant	Intron 1 of 25		XP_005248326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.-361+38654A>G		intron_variant	Intron 1 of 24	1	NM_178140.4	ENSP00000402033.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32991 AN: 152074 Hom.: 3761 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.217 AC: 33014 AN: 152192 Hom.: 3769 Cov.: 32 AF XY: 0.212 AC XY: 15783 AN XY: 74426

African (AFR) AF: 0.233 AC: 9658 AN: 41504

American (AMR) AF: 0.206 AC: 3149 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3466

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5186

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4818

European-Finnish (FIN) AF: 0.158 AC: 1680 AN: 10606

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15590 AN: 68006

Other (OTH) AF: 0.250 AC: 528 AN: 2116

Alfa AF: 0.228 Hom.: 17885

Bravo AF: 0.220

Asia WGS AF: 0.116 AC: 408 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	2.9
DANN	Benign	0.32
PhyloP100		0.26
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: rs4867365; hg19: chr5-31678198;