rs2226462

Variant names:

• chr3-38027267-C-T
• rs2226462
• NM_006225.4:c.34+2239G>A

Variant summary

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

The NM_006225.4(PLCD1):​c.34+2239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,060 control chromosomes in the GnomAD database, including 42,523 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 0.74 (42523 hom., cov: 32)
• Consequence: PLCD1 NM_006225.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 5 publications found

Genes affected

PLCD1 (HGNC:9060): (phospholipase C delta 1) This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

PLCD1 Gene-Disease associations (from GenCC):

• nonsyndromic congenital nail disorder 3

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000300099 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006225.4. 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
	PLCD1	NM_006225.4	MANE Select	c.34+2239G>A		intron	N/A	NP_006216.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD1	ENST00000334661.5	TSL:1 MANE Select	c.34+2239G>A		intron	N/A	ENSP00000335600.4
	PLCD1	ENST00000461445.5	TSL:2	n.54+2239G>A		intron	N/A
	ENSG00000300099	ENST00000768779.1		n.58+2554C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112544 AN: 151942 Hom.: 42476 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.741 AC: 112649 AN: 152060 Hom.: 42523 Cov.: 32 AF XY: 0.741 AC XY: 55047 AN XY: 74314

African (AFR) AF: 0.889 AC: 36883 AN: 41510

American (AMR) AF: 0.621 AC: 9481 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2212 AN: 3464

East Asian (EAS) AF: 0.629 AC: 3252 AN: 5174

South Asian (SAS) AF: 0.797 AC: 3843 AN: 4822

European-Finnish (FIN) AF: 0.673 AC: 7110 AN: 10560

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47489 AN: 67944

Other (OTH) AF: 0.734 AC: 1550 AN: 2112

Alfa AF: 0.717 Hom.: 20136

Bravo AF: 0.740

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.75
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: rs2226462; hg19: chr3-38068758;