Variant rs2232659 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_015916.5(CALHM2):c.286G>A(p.Ala96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,613,810 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 41 hom., cov: 32)

Exomes 𝑓: 0.020 ( 427 hom. )

Consequence

CALHM2
NM_015916.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

CALHM2 (HGNC:23493): (calcium homeostasis modulator family member 2) Predicted to enable cation channel activity. Involved in positive regulation of apoptotic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CALHM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025753677).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0168 (2564/152324) while in subpopulation SAS AF= 0.0201 (97/4830). AF 95% confidence interval is 0.019. There are 41 homozygotes in gnomad4. There are 1374 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALHM2	NM_015916.5 linkuse as main transcript	c.286G>A	p.Ala96Thr	missense_variant	3/4	ENST00000260743.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALHM2	ENST00000260743.10 linkuse as main transcript	c.286G>A	p.Ala96Thr	missense_variant	3/4	1	NM_015916.5	P1	Q9HA72-1
CALHM2	ENST00000369788.7 linkuse as main transcript	c.286G>A	p.Ala96Thr	missense_variant	3/4	2		P1	Q9HA72-1
CALHM2	ENST00000494180.1 linkuse as main transcript	n.934G>A		non_coding_transcript_exon_variant	2/2	2
CALHM2	ENST00000463878.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2565

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0217

AC:

5462

AN:

251274

Hom.:

127

AF XY:

0.0225

AC XY:

3061

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00916

Gnomad ASJ exome

AF:

0.0316

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.0641

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0198

AC:

28995

AN:

1461486

Hom.:

427

Cov.:

AF XY:

0.0201

AC XY:

14609

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00349

Gnomad4 AMR exome

AF:

0.00872

Gnomad4 ASJ exome

AF:

0.0328

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0208

Gnomad4 FIN exome

AF:

0.0626

Gnomad4 NFE exome

AF:

0.0190

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0168

AC:

2564

AN:

152324

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1374

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0586

Gnomad4 NFE

AF:

0.0199

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0126

TwinsUK

AF:

0.0173

AC:

ALSPAC

AF:

0.0169

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0195

AC:

168

ExAC

AF:

0.0212

AC:

2577

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.53

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.031

Sift

Benign

0.47

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.010

B;B

Vest4

0.13

MPC

0.21

ClinPred

0.014

GERP RS

5.5

Varity_R

0.069

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over