1-2479937-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014638.4(PLCH2):c.475G>A(p.Asp159Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,609,054 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: PLCH2 NM_014638.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.62

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0080688).
• BP6: Variant 1-2479937-G-A is Benign according to our data. Variant chr1-2479937-G-A is described in ClinVar as [Benign]. Clinvar id is 713841.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	NM_014638.4	c.475G>A	p.Asp159Asn	missense_variant	3/22	ENST00000378486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH2	ENST00000378486.8	c.475G>A	p.Asp159Asn	missense_variant	3/22	1	NM_014638.4	P2

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 224 AN: 152196 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00979

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00167 AC: 396 AN: 237670 Hom.: 2 AF XY: 0.00173 AC XY: 227 AN XY: 130838

Gnomad AFR exome AF: 0.000353

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000592

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00174 AC: 2539 AN: 1456858 Hom.: 6 Cov.: 30 AF XY: 0.00170 AC XY: 1232 AN XY: 724260

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000836

Gnomad4 FIN exome AF: 0.00969

Gnomad4 NFE exome AF: 0.00167

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152196 Hom.: 1 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74356

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00979

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000763

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000697 AC: 3

ESP6500EA AF: 0.00130 AC: 11

ExAC AF: 0.00144 AC: 173

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.53
Cadd	Pathogenic	26
Dann	Uncertain	0.99
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.0081	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Benign	0.20
Sift	Benign	0.21	T;.;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.95	.;P;P
Vest4		0.68
MVP		0.39
MPC		0.77
ClinPred		0.062	T
GERP RS		4.9
Varity_R		0.23
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs200040569; hg19: chr1-2411376; COSMIC: COSV99617640; COSMIC: COSV99617640;