rs500557

Variant names:

• chr5-31758844-C-G
• rs500557
• NM_178140.4:c.-360-40045C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-31758844-C-G
• chr5-31758844-C-T

Variant summary

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

The NM_178140.4(PDZD2):​c.-360-40045C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,874 control chromosomes in the GnomAD database, including 22,970 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 0.54 (22970 hom., cov: 31)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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.-360-40045C>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.-360-40045C>G		intron	N/A	ENSP00000402033.1	O15018-1
	PDZD2	ENST00000502824.1	TSL:1	n.89-40045C>G		intron	N/A
	PDZD2	ENST00000942338.1		c.-360-40045C>G		intron	N/A	ENSP00000612397.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82576 AN: 151756 Hom.: 22961 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.544 AC: 82622 AN: 151874 Hom.: 22970 Cov.: 31 AF XY: 0.541 AC XY: 40131 AN XY: 74212

African (AFR) AF: 0.552 AC: 22833 AN: 41390

American (AMR) AF: 0.651 AC: 9939 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1588 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4367 AN: 5138

South Asian (SAS) AF: 0.508 AC: 2446 AN: 4812

European-Finnish (FIN) AF: 0.427 AC: 4499 AN: 10540

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35187 AN: 67946

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.534 Hom.: 2719

Bravo AF: 0.565

Asia WGS AF: 0.662 AC: 2301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.83
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: rs500557; hg19: chr5-31758951;