Variant 10-103449426-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015916.5(CALHM2):c.516C>G(p.Phe172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CALHM2
NM_015916.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

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:

CALHM2 (HGNC:):

CALHM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23637295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM2	NM_015916.5 linkuse as main transcript	c.516C>G	p.Phe172Leu	missense_variant	3/4	ENST00000260743.10	NP_057000.2	Q9HA72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM2	ENST00000260743.10 linkuse as main transcript	c.516C>G	p.Phe172Leu	missense_variant	3/4	1	NM_015916.5	ENSP00000260743.5		Q9HA72-1
CALHM2	ENST00000369788.7 linkuse as main transcript	c.516C>G	p.Phe172Leu	missense_variant	3/4	2		ENSP00000358803.3		Q9HA72-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249350

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135318

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000459

AC:

AN:

1460852

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000849

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.516C>G (p.F172L) alteration is located in exon 3 (coding exon 1) of the CALHM2 gene. This alteration results from a C to G substitution at nucleotide position 516, causing the phenylalanine (F) at amino acid position 172 to be replaced by a leucine (L). 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

0.68

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.094

Sift

Benign

0.20

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0030

B;B

Vest4

0.52

MutPred

0.25

Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);

MVP

0.32

MPC

0.54

ClinPred

0.48

GERP RS

3.5

Varity_R

0.28

gMVP

0.49

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over