2-218618759-T-C

Position:

• chr2-218618759-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032726.4(PLCD4):​c.362T>C​(p.Leu121Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PLCD4 NM_032726.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.871

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCD4	NM_032726.4	c.362T>C	p.Leu121Pro	missense_variant	4/16	ENST00000450993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCD4	ENST00000450993.7	c.362T>C	p.Leu121Pro	missense_variant	4/16	1	NM_032726.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1454830 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 723026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.362T>C (p.L121P) alteration is located in exon 4 (coding exon 3) of the PLCD4 gene. This alteration results from a T to C substitution at nucleotide position 362, causing the leucine (L) at amino acid position 121 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T;.;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	0.89	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.32	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.052	T;T;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.84	P;P;.
Vest4		0.72
MutPred		0.51		Loss of stability (P = 0.0342);Loss of stability (P = 0.0342);Loss of stability (P = 0.0342);
MVP		0.71
MPC		0.99
ClinPred		0.45	T
GERP RS		2.4
Varity_R		0.12
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219483482;