dbSNP rs3747354: EFHC2:p.Glu507Gln (chrX-44232582-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025184.4(EFHC2):c.1519G>C(p.Glu507Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00509 in 1,193,311 control chromosomes in the GnomAD database, including 127 homozygotes. There are 1,864 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., 260 hem., cov: 23)

Exomes 𝑓: 0.0050 ( 120 hom. 1604 hem. )

Consequence

EFHC2
NM_025184.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.33

Publications

5 publications found

Variant links:

Genes affected

EFHC2 (HGNC:26233): (EF-hand domain containing 2) This gene encodes a protein which contains three DM10 domains and three calcium-binding EF-hand motifs. A related protein is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy (PMID: 15258581, 16112844) and that this gene may be associated with fear recognition in individuals with Turner syndrome. [provided by RefSeq, Aug 2011]

EFHC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062425435).

BP6

Variant X-44232582-C-G is Benign according to our data. Variant chrX-44232582-C-G is described in ClinVar as Benign. ClinVar VariationId is 193745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC2	NM_025184.4	MANE Select	c.1519G>C	p.Glu507Gln	missense	Exon 10 of 15	NP_079460.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFHC2	ENST00000420999.2	TSL:1 MANE Select	c.1519G>C	p.Glu507Gln	missense	Exon 10 of 15	ENSP00000404232.2	Q5JST6-1
EFHC2	ENST00000937700.1		c.1519G>C	p.Glu507Gln	missense	Exon 10 of 14	ENSP00000607759.1
EFHC2	ENST00000889038.1		c.1393G>C	p.Glu465Gln	missense	Exon 10 of 15	ENSP00000559097.1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

717

AN:

111967

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0745

Gnomad SAS

AF:

0.00225

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00667

GnomAD2 exomes

AF:

0.0128

AC:

1922

AN:

150593

AF XY:

0.0104

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0770

Gnomad FIN exome

AF:

0.00760

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00872

GnomAD4 exome

AF:

0.00495

AC:

5357

AN:

1081291

Hom.:

120

Cov.:

AF XY:

0.00457

AC XY:

1604

AN XY:

351183

show subpopulations

African (AFR)

AF:

0.000841

AC:

AN:

26153

American (AMR)

AF:

0.0346

AC:

1143

AN:

33048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18967

East Asian (EAS)

AF:

0.0888

AC:

2641

AN:

29726

South Asian (SAS)

AF:

0.00156

AC:

AN:

51160

European-Finnish (FIN)

AF:

0.00680

AC:

269

AN:

39585

Middle Eastern (MID)

AF:

0.00268

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.00110

AC:

916

AN:

833044

Other (OTH)

AF:

0.00604

AC:

275

AN:

45501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

188

377

565

754

942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00643

AC:

720

AN:

112020

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

260

AN XY:

34198

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

30861

American (AMR)

AF:

0.0250

AC:

265

AN:

10585

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.0747

AC:

266

AN:

3559

South Asian (SAS)

AF:

0.00226

AC:

AN:

2657

European-Finnish (FIN)

AF:

0.00923

AC:

AN:

6069

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

53215

Other (OTH)

AF:

0.00658

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00372

Hom.:

Bravo

AF:

0.00815

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00138

AC:

ExAC

AF:

0.00947

AC:

1134

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

PhyloP100

5.3

PrimateAI

Benign

0.41

REVEL

Benign

0.20

Sift4G

Uncertain

0.010

Polyphen

0.26

Vest4

0.11

MPC

0.19

ClinPred

0.0098

GERP RS

5.8

Varity_R

0.29

gMVP

0.84

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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