Variant 7-93215506-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001039372.4(HEPACAM2):c.610C>T(p.Leu204Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00188 in 1,613,860 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 30 hom. )

Consequence

HEPACAM2
NM_001039372.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006296903).

BP6

Variant 7-93215506-G-A is Benign according to our data. Variant chr7-93215506-G-A is described in ClinVar as [Benign]. Clinvar id is 776240.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0093 (1415/152232) while in subpopulation AFR AF= 0.0308 (1278/41534). AF 95% confidence interval is 0.0294. There are 18 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM2	NM_001039372.4 linkuse as main transcript	c.610C>T	p.Leu204Phe	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.610C>T	p.Leu204Phe	missense_variant	3/10	2	NM_001039372.4	ENSP00000377980.2	A8MVW5-1
HEPACAM2	ENST00000440868.5 linkuse as main transcript	c.574C>T	p.Leu192Phe	missense_variant	2/8	1		ENSP00000389592.1	C9JN07
HEPACAM2	ENST00000341723.8 linkuse as main transcript	c.574C>T	p.Leu192Phe	missense_variant	2/9	1		ENSP00000340532.4	A8MVW5-2
HEPACAM2	ENST00000453812.2 linkuse as main transcript	c.679C>T	p.Leu227Phe	missense_variant	4/11	2		ENSP00000390204.2	A8MVW5-3

Frequencies

GnomAD3 genomes

AF:

0.00929

AC:

1413

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00734

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00239

AC:

601

AN:

251268

Hom.:

AF XY:

0.00177

AC XY:

241

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0326

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00111

AC:

1620

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000908

AC XY:

660

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0361

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00930

AC:

1415

AN:

152232

Hom.:

Cov.:

AF XY:

0.00949

AC XY:

706

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.00733

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.0117

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00277

AC:

336

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

.;.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.0063

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.7

.;.;M;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.46

Sift

Benign

0.071

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.23

B;B;B;.

Vest4

0.32

MVP

0.71

MPC

0.15

ClinPred

0.054

GERP RS

2.6

Varity_R

0.21

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over