7-93192348-C-A

Position:

• chr7-93192348-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13990968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM2	NM_001039372.4	c.1291G>T	p.Val431Phe	missense_variant	9/10	ENST00000394468.7	NP_001034461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM2	ENST00000394468.7	c.1291G>T	p.Val431Phe	missense_variant	9/10	2	NM_001039372.4	ENSP00000377980.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.1291G>T (p.V431F) alteration is located in exon 9 (coding exon 9) of the HEPACAM2 gene. This alteration results from a G to T substitution at nucleotide position 1291, causing the valine (V) at amino acid position 431 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.037
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.76	P;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92821661;