rs11957407

Variant names:

• chr5-31917136-G-A
• rs11957407
• NM_178140.4:c.477-66019G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000438447.2(PDZD2):​c.477-66019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,300 control chromosomes in the GnomAD database, including 19 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 0.011 (19 hom., cov: 32)
• Consequence: PDZD2 ENST00000438447.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 1746 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438447.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD2	NM_178140.4	MANE Select	c.477-66019G>A		intron	N/A	NP_835260.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD2	ENST00000438447.2	TSL:1 MANE Select	c.477-66019G>A		intron	N/A	ENSP00000402033.1
	PDZD2	ENST00000502489.5	TSL:2	n.232+61968G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1746 AN: 152182 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.00431

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

GnomAD4 genome AF: 0.0115 AC: 1746 AN: 152300 Hom.: 19 Cov.: 32 AF XY: 0.0118 AC XY: 877 AN XY: 74464

African (AFR) AF: 0.00238 AC: 99 AN: 41562

American (AMR) AF: 0.0115 AC: 176 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.0364 AC: 386 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 999 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.0130 Hom.: 5

Bravo AF: 0.00943

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.71
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism

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: rs11957407; hg19: chr5-31917242;