5-32107658-T-G

Variant names:

• chr5-32107658-T-G
• rs161522
• NM_178140.4:c.8354-311T>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.8354-311T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,140 control chromosomes in the GnomAD database, including 47,408 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 0.79 (47408 hom., cov: 33)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 4 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]

LOC105374711 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178140.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD2	NM_178140.4	MANE Select	c.8354-311T>G		intron	N/A	NP_835260.2	O15018-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD2	ENST00000438447.2	TSL:1 MANE Select	c.8354-311T>G		intron	N/A	ENSP00000402033.1	O15018-1
	PDZD2	ENST00000397559.3	TSL:1	n.98-311T>G		intron	N/A
	PDZD2	ENST00000510285.1	TSL:1	n.140+198T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119892 AN: 152022 Hom.: 47387 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.788 AC: 119953 AN: 152140 Hom.: 47408 Cov.: 33 AF XY: 0.786 AC XY: 58477 AN XY: 74394

African (AFR) AF: 0.775 AC: 32147 AN: 41480

American (AMR) AF: 0.805 AC: 12300 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2653 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3733 AN: 5176

South Asian (SAS) AF: 0.756 AC: 3637 AN: 4810

European-Finnish (FIN) AF: 0.795 AC: 8418 AN: 10588

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54447 AN: 68004

Other (OTH) AF: 0.771 AC: 1632 AN: 2116

Alfa AF: 0.795 Hom.: 99002

Bravo AF: 0.791

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		1.1
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: rs161522; hg19: chr5-32107764;