chr10-103447481-G-T

Variant names:

• chr10-103447481-G-T
• rs753123584
• NM_015916.5:c.643C>A

Variant summary

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

The NM_015916.5(CALHM2):​c.643C>A​(p.Arg215Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R215C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALHM2 NM_015916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.89
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015916.5. 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
	CALHM2	NM_015916.5	MANE Select	c.643C>A	p.Arg215Ser	missense	Exon 4 of 4	NP_057000.2
	CALHM2	NR_024552.2		n.1103C>A		non_coding_transcript_exon	Exon 4 of 4
	CALHM2	NR_046344.2		n.1116C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM2	ENST00000260743.10	TSL:1 MANE Select	c.643C>A	p.Arg215Ser	missense	Exon 4 of 4	ENSP00000260743.5	Q9HA72-1
	CALHM2	ENST00000369788.7	TSL:2	c.643C>A	p.Arg215Ser	missense	Exon 4 of 4	ENSP00000358803.3	Q9HA72-1
	CALHM2	ENST00000882006.1		c.643C>A	p.Arg215Ser	missense	Exon 5 of 5	ENSP00000552065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.13
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Polyphen		0.22	B
Vest4		0.65
MutPred		0.52		Gain of disorder (P = 0.0678)
MVP		0.30
MPC		0.51
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.63
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs753123584; hg19: chr10-105207238;