2-218615966-T-G

Variant names:

• chr2-218615966-T-G
• rs1575015608
• NM_032726.4:c.85T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032726.4(PLCD4):​c.85T>G​(p.Ser29Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S29P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37555873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.85T>G	p.Ser29Ala	missense_variant	Exon 3 of 16	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.85T>G	p.Ser29Ala	missense_variant	Exon 3 of 16	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.85T>G	p.Ser29Ala	missense_variant	Exon 3 of 17	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.85T>G	p.Ser29Ala	missense_variant	Exon 3 of 17	5		ENSP00000396942.1
PLCD4	ENST00000444453.5	n.78+7T>G		splice_region_variant, intron_variant	Intron 3 of 4	4		ENSP00000415725.1
PLCD4	ENST00000446503.5	n.78+7T>G		splice_region_variant, intron_variant	Intron 3 of 5	4		ENSP00000406040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.8	M;M;.;.
PhyloP100		3.9
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.4	N;N;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		0.96	D;D;.;.
Vest4		0.18
MutPred		0.39		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.82
MPC		0.52
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.30
gMVP		0.35
Mutation Taster		=86/14	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: rs1575015608; hg19: chr2-219480689;