chr7-93192348-C-A

Variant names:

• chr7-93192348-C-A
• NM_001039372.4:c.1291G>T

Variant summary

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

The NM_001039372.4(HEPACAM2):​c.1291G>T​(p.Val431Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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: -0.510
• 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: 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=0.13990968).

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.1291G>T	p.Val431Phe	missense	Exon 9 of 10	NP_001034461.1	A8MVW5-1
	HEPACAM2	NM_001288804.3		c.1360G>T	p.Val454Phe	missense	Exon 10 of 11	NP_001275733.1	A8MVW5-3
	HEPACAM2	NM_198151.4		c.1255G>T	p.Val419Phe	missense	Exon 8 of 9	NP_937794.1	A8MVW5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM2	ENST00000394468.7	TSL:2 MANE Select	c.1291G>T	p.Val431Phe	missense	Exon 9 of 10	ENSP00000377980.2	A8MVW5-1
	HEPACAM2	ENST00000341723.8	TSL:1	c.1255G>T	p.Val419Phe	missense	Exon 8 of 9	ENSP00000340532.4	A8MVW5-2
	HEPACAM2	ENST00000440868.5	TSL:1	c.1230G>T	p.Leu410Leu	synonymous	Exon 7 of 8	ENSP00000389592.1	C9JN07

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.074
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.1
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.51
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.037
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.027	D
Polyphen		0.76	P
Vest4		0.43
MutPred		0.32		Loss of catalytic residue at V431 (P = 0.0816)
MVP		0.19
MPC		0.23
ClinPred		0.22	T
GERP RS		0.15
Varity_R		0.095
gMVP		0.59
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-92821661;