Genetic Variant HEPACAM2:p.Leu204Phe (chr7-93215506-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

HEPACAM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 Unknown gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEPACAM2	NM_001039372.4	MANE Select	c.610C>T	p.Leu204Phe	missense	Exon 3 of 10	NP_001034461.1	A8MVW5-1
HEPACAM2	NM_001288804.3		c.679C>T	p.Leu227Phe	missense	Exon 4 of 11	NP_001275733.1	A8MVW5-3
HEPACAM2	NM_001288810.3		c.574C>T	p.Leu192Phe	missense	Exon 2 of 8	NP_001275739.1	C9JN07

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEPACAM2	ENST00000394468.7	TSL:2 MANE Select	c.610C>T	p.Leu204Phe	missense	Exon 3 of 10	ENSP00000377980.2	A8MVW5-1
HEPACAM2	ENST00000440868.5	TSL:1	c.574C>T	p.Leu192Phe	missense	Exon 2 of 8	ENSP00000389592.1	C9JN07
HEPACAM2	ENST00000341723.8	TSL:1	c.574C>T	p.Leu192Phe	missense	Exon 2 of 9	ENSP00000340532.4	A8MVW5-2

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

GnomAD2 exomes

AF:

0.00239

AC:

601

AN:

251268

AF XY:

0.00177

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 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

African (AFR)

AF:

0.0361

AC:

1209

AN:

33458

American (AMR)

AF:

0.00208

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000139

AC:

155

AN:

1111854

Other (OTH)

AF:

0.00248

AC:

150

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

179

269

358

448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00930

AC:

1415

AN:

152232

Hom.:

Cov.:

AF XY:

0.00949

AC XY:

706

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0308

AC:

1278

AN:

41534

American (AMR)

AF:

0.00733

AC:

112

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

150

225

300

375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00348

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

0.022

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.7

PhyloP100

3.8

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.46

Sift

Benign

0.071

Sift4G

Benign

0.23

Polyphen

0.23

Vest4

0.32

MVP

0.71

MPC

0.15

ClinPred

0.054

GERP RS

2.6

Varity_R

0.21

gMVP

0.79

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over