Genetic Variant HCAR2:p.Val292Leu (chr12-122702410-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_177551.4(HCAR2):c.874G>C(p.Val292Leu) 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. 16/22 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. V292M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

HCAR2
NM_177551.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.80

Publications

2 publications found

Variant links:

Genes affected

HCAR2 (HGNC:24827): (hydroxycarboxylic acid receptor 2) Predicted to enable nicotinic acid receptor activity. Involved in neutrophil apoptotic process and positive regulation of neutrophil apoptotic process. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HCAR2 links:

ENSG00000256249 (HGNC:):

ENSG00000256249 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05043274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177551.4. 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
	HCAR2	NM_177551.4	MANE Select	c.874G>C	p.Val292Leu	missense	Exon 1 of 1	NP_808219.1	Q8TDS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCAR2	ENST00000328880.6	TSL:6 MANE Select	c.874G>C	p.Val292Leu	missense	Exon 1 of 1	ENSP00000375066.2	Q8TDS4
	ENSG00000256249	ENST00000543611.1	TSL:4	n.401+1080C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250500

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0070

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.091

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.48

M_CAP

Benign

0.0045

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.74

PhyloP100

-2.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

REVEL

Benign

0.099

Sift

Benign

1.0

Sift4G

Benign

0.92

Polyphen

0.0020

Vest4

0.023

MutPred

0.50

Loss of sheet (P = 0.1398)

MVP

0.20

MPC

0.73

ClinPred

0.052

GERP RS

-12

Varity_R

0.069

gMVP

0.14

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over