chr2-218615954-C-T

Variant names:

• chr2-218615954-C-T
• rs186920731
• NM_032726.4:c.73C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_032726.4(PLCD4):​c.73C>T​(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R25H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• Publications: 1 publications found

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2677815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032726.4. 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
	PLCD4	NM_032726.4	MANE Select	c.73C>T	p.Arg25Cys	missense	Exon 3 of 16	NP_116115.1	Q9BRC7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD4	ENST00000450993.7	TSL:1 MANE Select	c.73C>T	p.Arg25Cys	missense	Exon 3 of 16	ENSP00000388631.2	Q9BRC7-1
	PLCD4	ENST00000432688.5	TSL:5	c.73C>T	p.Arg25Cys	missense	Exon 3 of 17	ENSP00000396185.1	C9JEA7
	PLCD4	ENST00000417849.5	TSL:5	c.73C>T	p.Arg25Cys	missense	Exon 3 of 17	ENSP00000396942.1	Q9BRC7-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249250 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111870

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74468

African (AFR) AF: 0.0000963 AC: 4 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.000243 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000413 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Benign	0.82
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.36
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.48
MVP		0.73
MPC		0.97
ClinPred		0.64	D
GERP RS		3.2
Varity_R		0.11
gMVP		0.73
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs186920731; hg19: chr2-219480677;