chr10-103449529-G-A

Variant names:

• chr10-103449529-G-A
• NM_015916.5:c.413C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015916.5(CALHM2):​c.413C>T​(p.Pro138Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALHM2 NM_015916.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.66
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3449198).

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.413C>T	p.Pro138Leu	missense	Exon 3 of 4	NP_057000.2
	CALHM2	NR_024552.2		n.886C>T		non_coding_transcript_exon	Exon 3 of 4
	CALHM2	NR_046344.2		n.886C>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM2	ENST00000260743.10	TSL:1 MANE Select	c.413C>T	p.Pro138Leu	missense	Exon 3 of 4	ENSP00000260743.5	Q9HA72-1
	CALHM2	ENST00000369788.7	TSL:2	c.413C>T	p.Pro138Leu	missense	Exon 3 of 4	ENSP00000358803.3	Q9HA72-1
	CALHM2	ENST00000882006.1		c.413C>T	p.Pro138Leu	missense	Exon 4 of 5	ENSP00000552065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		8.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.11	B
Vest4		0.66
MutPred		0.40		Loss of disorder (P = 0.0389)
MVP		0.34
MPC		0.79
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.31
gMVP		0.73
Mutation Taster		=39/61	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

hg19: chr10-105209286;