rs777286891

Variant names:

• chr1-2476632-C-A
• rs777286891
• NM_014638.4:c.44C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-2476632-C-A
• chr1-2476632-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014638.4(PLCH2):​c.44C>A​(p.Thr15Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. T15M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCH2 NM_014638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 2 publications found

Genes affected

PLCH2 (HGNC:29037): (phospholipase C eta 2) PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11563519).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014638.4. 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
	PLCH2	NM_014638.4	MANE Select	c.44C>A	p.Thr15Lys	missense	Exon 1 of 22	NP_055453.2
	PLCH2	NM_001303013.1		c.-889C>A		5_prime_UTR	Exon 1 of 22	NP_001289942.1	O75038
	PLCH2	NM_001303012.2		c.44-1844C>A		intron	N/A	NP_001289941.1	O75038-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH2	ENST00000378486.8	TSL:1 MANE Select	c.44C>A	p.Thr15Lys	missense	Exon 1 of 22	ENSP00000367747.3	O75038-1
	PLCH2	ENST00000419816.6	TSL:5	c.44C>A	p.Thr15Lys	missense	Exon 1 of 22	ENSP00000389803.2	O75038-1
	PLCH2	ENST00000449969.5	TSL:5	c.44-1844C>A		intron	N/A	ENSP00000397289.1	O75038-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.029
Sift	Benign	0.034	D
Sift4G	Benign	0.065	T
Polyphen		0.53	P
Vest4		0.23
MutPred		0.47		Gain of ubiquitination at T15 (P = 0.0219)
MVP		0.28
ClinPred		0.20	T
GERP RS		2.1
PromoterAI		-0.014	Neutral
Varity_R		0.15
gMVP		0.43
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs777286891; hg19: chr1-2408071;