Genetic Variant HEPACAM2:p.Cys367Ser (chr7-93197523-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039372.4(HEPACAM2):c.1100G>C(p.Cys367Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.9e-7 ( 0 hom. )

Consequence

HEPACAM2
NM_001039372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.546

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.13648373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPACAM2	NM_001039372.4 link	c.1100G>C	p.Cys367Ser	missense_variant	Exon 5 of 10	ENST00000394468.7	NP_001034461.1	A8MVW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPACAM2	ENST00000394468.7 link	c.1100G>C	p.Cys367Ser	missense_variant	Exon 5 of 10	2	NM_001039372.4	ENSP00000377980.2		A8MVW5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443034

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1100G>C (p.C367S) alteration is located in exon 5 (coding exon 5) of the HEPACAM2 gene. This alteration results from a G to C substitution at nucleotide position 1100, causing the cysteine (C) at amino acid position 367 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.011

.;.;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

.;.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.64

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0050

B;B;B;.

Vest4

0.27

MutPred

0.51

.;.;Loss of sheet (P = 0.0054);.;

MVP

0.32

MPC

0.14

ClinPred

0.13

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.42

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over