NM_001039372.4:c.943T>G

Variant names:

• chr7-93208649-A-C
• rs1794092431
• NM_001039372.4:c.943T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001039372.4(HEPACAM2):​c.943T>G​(p.Cys315Gly) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEPACAM2 NM_001039372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.04
• Publications: 0 publications found

Genes affected

HEPACAM2 (HGNC:27364): (HEPACAM family member 2) This gene encodes a protein related to the immunoglobulin superfamily that plays a role in mitosis. Knockdown of this gene results in prometaphase arrest, abnormal nuclear morphology and apoptosis. Poly(ADP-ribosylation) of the encoded protein promotes its translocation to centrosomes, which may stimulate centrosome maturation. A chromosomal deletion including this gene may be associated with myeloid leukemia and myelodysplastic syndrome in human patients. [provided by RefSeq, Oct 2016]

HEPACAM2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039372.4. 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
	HEPACAM2	NM_001039372.4	MANE Select	c.943T>G	p.Cys315Gly	missense	Exon 4 of 10	NP_001034461.1	A8MVW5-1
	HEPACAM2	NM_001288804.3		c.1012T>G	p.Cys338Gly	missense	Exon 5 of 11	NP_001275733.1	A8MVW5-3
	HEPACAM2	NM_001288810.3		c.907T>G	p.Cys303Gly	missense	Exon 3 of 8	NP_001275739.1	C9JN07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM2	ENST00000394468.7	TSL:2 MANE Select	c.943T>G	p.Cys315Gly	missense	Exon 4 of 10	ENSP00000377980.2	A8MVW5-1
	HEPACAM2	ENST00000440868.5	TSL:1	c.907T>G	p.Cys303Gly	missense	Exon 3 of 8	ENSP00000389592.1	C9JN07
	HEPACAM2	ENST00000341723.8	TSL:1	c.907T>G	p.Cys303Gly	missense	Exon 3 of 9	ENSP00000340532.4	A8MVW5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		8.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.84		Loss of catalytic residue at M311 (P = 0.0725)
MVP		0.73
MPC		0.62
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.97
Mutation Taster		=10/90	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: rs1794092431; hg19: chr7-92837962;