Variant X-44235320-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000420999.2(EFHC2):c.1408A>G(p.Ile470Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,179,785 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I470M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 0 hom. 38 hem. )

Consequence

EFHC2
ENST00000420999.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.409

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026543736).

BP6

Variant X-44235320-T-C is Benign according to our data. Variant chrX-44235320-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660364.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFHC2	NM_025184.4 linkuse as main transcript	c.1408A>G	p.Ile470Val	missense_variant	9/15	ENST00000420999.2	NP_079460.2
EFHC2	XM_047442535.1 linkuse as main transcript	c.1408A>G	p.Ile470Val	missense_variant	9/14		XP_047298491.1
EFHC2	XM_047442536.1 linkuse as main transcript	c.1408A>G	p.Ile470Val	missense_variant	9/15		XP_047298492.1
EFHC2	XM_006724562.3 linkuse as main transcript	c.820A>G	p.Ile274Val	missense_variant	8/14		XP_006724625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC2	ENST00000420999.2 linkuse as main transcript	c.1408A>G	p.Ile470Val	missense_variant	9/15	1	NM_025184.4	ENSP00000404232	P1	Q5JST6-1

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

AN XY:

33706

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000289

AC:

AN:

134847

Hom.:

AF XY:

0.000249

AC XY:

AN XY:

36201

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00348

Gnomad SAS exome

AF:

0.000153

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

125

AN:

1068206

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

343994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00337

Gnomad4 SAS exome

AF:

0.000284

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000484

Gnomad4 OTH exome

AF:

0.000178

GnomAD4 genome

AF:

0.000152

AC:

AN:

111579

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

33771

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00455

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000317

ExAC

AF:

0.000349

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

EFHC2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.85

DANN

Benign

0.40

DEOGEN2

Benign

0.0013

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.62

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

REVEL

Benign

0.017

Sift4G

Benign

0.96

Polyphen

0.0020

Vest4

0.0080

MVP

0.043

MPC

0.072

ClinPred

0.0073

GERP RS

-1.1

Varity_R

0.041

gMVP

0.45

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

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