NM_015916.5:c.286G>T

Variant names:

• chr10-103449656-C-A
• rs2232659
• NM_015916.5:c.286G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015916.5(CALHM2):​c.286G>T​(p.Ala96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CALHM2 NM_015916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10396537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM2	NM_015916.5	c.286G>T	p.Ala96Ser	missense_variant	Exon 3 of 4	ENST00000260743.10	NP_057000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM2	ENST00000260743.10	c.286G>T	p.Ala96Ser	missense_variant	Exon 3 of 4	1	NM_015916.5	ENSP00000260743.5
CALHM2	ENST00000369788.7	c.286G>T	p.Ala96Ser	missense_variant	Exon 3 of 4	2		ENSP00000358803.3
CALHM2	ENST00000494180.1	n.934G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
CALHM2	ENST00000463878.1	n.*43G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461490 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0060	T;T
Eigen	Benign	0.042
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		2.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.022
Sift	Benign	0.48	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.018	B;B
Vest4		0.16
MutPred		0.31		Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);
MVP		0.19
MPC		0.31
ClinPred		0.34	T
GERP RS		5.5
Varity_R		0.082
gMVP		0.47
Mutation Taster		=76/24	polymorphism

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: rs2232659; hg19: chr10-105209413;