rs6450864

Variant names:

• chr5-31787274-T-C
• rs6450864
• NM_178140.4:c.-360-11615T>C

Variant summary

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

The NM_178140.4(PDZD2):​c.-360-11615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,292 control chromosomes in the GnomAD database, including 804 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 0.099 (804 hom., cov: 32)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD2	NM_178140.4	c.-360-11615T>C		intron_variant	Intron 1 of 24	ENST00000438447.2	NP_835260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD2	ENST00000438447.2	c.-360-11615T>C		intron_variant	Intron 1 of 24	1	NM_178140.4	ENSP00000402033.1
PDZD2	ENST00000502824.1	n.89-11615T>C		intron_variant	Intron 1 of 2	1
PDZD2	ENST00000513910.1	c.-442-363T>C		intron_variant	Intron 1 of 2	3		ENSP00000424901.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15018 AN: 152174 Hom.: 803 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0988 AC: 15040 AN: 152292 Hom.: 804 Cov.: 32 AF XY: 0.102 AC XY: 7611 AN XY: 74480

African (AFR) AF: 0.0826 AC: 3434 AN: 41560

American (AMR) AF: 0.0775 AC: 1185 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3468

East Asian (EAS) AF: 0.121 AC: 626 AN: 5186

South Asian (SAS) AF: 0.178 AC: 860 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1308 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0991 AC: 6738 AN: 68024

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0964 Hom.: 1238

Bravo AF: 0.0906

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		-0.37
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: rs6450864; hg19: chr5-31787381;