Variant chr7-93215628-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039372.4(HEPACAM2):c.488T>C(p.Val163Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

HEPACAM2
NM_001039372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4153347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM2	NM_001039372.4 linkuse as main transcript	c.488T>C	p.Val163Ala	missense_variant	3/10	ENST00000394468.7	NP_001034461.1	A8MVW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HEPACAM2	ENST00000394468.7 linkuse as main transcript	c.488T>C	p.Val163Ala	missense_variant	3/10	2	NM_001039372.4	ENSP00000377980.2	A8MVW5-1
HEPACAM2	ENST00000440868.5 linkuse as main transcript	c.452T>C	p.Val151Ala	missense_variant	2/8	1		ENSP00000389592.1	C9JN07
HEPACAM2	ENST00000341723.8 linkuse as main transcript	c.452T>C	p.Val151Ala	missense_variant	2/9	1		ENSP00000340532.4	A8MVW5-2
HEPACAM2	ENST00000453812.2 linkuse as main transcript	c.557T>C	p.Val186Ala	missense_variant	4/11	2		ENSP00000390204.2	A8MVW5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.488T>C (p.V163A) alteration is located in exon 3 (coding exon 3) of the HEPACAM2 gene. This alteration results from a T to C substitution at nucleotide position 488, causing the valine (V) at amino acid position 163 to be replaced by an alanine (A). 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

0.089

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00094

.;.;T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.98

.;.;L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.87

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.65

T;T;T;T

Sift4G

Uncertain

0.049

D;T;T;T

Polyphen

0.90

P;P;P;.

Vest4

0.51

MutPred

0.51

.;.;Loss of stability (P = 0.0941);.;

MVP

0.64

MPC

0.52

ClinPred

0.83

GERP RS

5.6

Varity_R

0.067

gMVP

0.47

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