3-111782338-G-C

Variant names:

• chr3-111782338-G-C
• rs3922704
• ENST00000477665.2:c.*33+49635G>C

Variant summary

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

The ENST00000477665.2(PLCXD2):​c.*33+49635G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,836 control chromosomes in the GnomAD database, including 4,581 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 0.24 (4581 hom., cov: 32)
• Consequence: PLCXD2 ENST00000477665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 5 publications found

Genes affected

PLCXD2 (HGNC:26462): (phosphatidylinositol specific phospholipase C X domain containing 2) Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB2	NM_001134437.2	c.-49+49635G>C		intron_variant	Intron 1 of 17		NP_001127909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCXD2	ENST00000477665.2	c.*33+49635G>C		intron_variant	Intron 4 of 4	1	NM_001185106.1	ENSP00000420686.1
PLCXD2	ENST00000393934.7	c.867-63483G>C		intron_variant	Intron 3 of 3	1		ENSP00000377511.3
PHLDB2	ENST00000393923.7	c.-49+49635G>C		intron_variant	Intron 1 of 17	2		ENSP00000377500.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35736 AN: 151718 Hom.: 4569 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.236 AC: 35776 AN: 151836 Hom.: 4581 Cov.: 32 AF XY: 0.231 AC XY: 17109 AN XY: 74202

African (AFR) AF: 0.331 AC: 13698 AN: 41364

American (AMR) AF: 0.182 AC: 2767 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.158 AC: 815 AN: 5160

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14489 AN: 67916

Other (OTH) AF: 0.206 AC: 434 AN: 2106

Alfa AF: 0.217 Hom.: 439

Bravo AF: 0.244

Asia WGS AF: 0.183 AC: 632 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.42
PhyloP100		0.13
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: rs3922704; hg19: chr3-111501185;