Variant chrX-44235338-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025184.4(EFHC2):c.1390A>G(p.Ile464Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,075,434 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

EFHC2
NM_025184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.376

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081977844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC2	NM_025184.4 linkuse as main transcript	c.1390A>G	p.Ile464Val	missense_variant	9/15	ENST00000420999.2	NP_079460.2	Q5JST6-1
EFHC2	XM_047442535.1 linkuse as main transcript	c.1390A>G	p.Ile464Val	missense_variant	9/14		XP_047298491.1
EFHC2	XM_047442536.1 linkuse as main transcript	c.1390A>G	p.Ile464Val	missense_variant	9/15		XP_047298492.1
EFHC2	XM_006724562.3 linkuse as main transcript	c.802A>G	p.Ile268Val	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.1390A>G	p.Ile464Val	missense_variant	9/15	1	NM_025184.4	ENSP00000404232.2		Q5JST6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000186

AC:

AN:

1075434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

348554

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:

0.00000241

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2024

The c.1390A>G (p.I464V) alteration is located in exon 9 (coding exon 9) of the EFHC2 gene. This alteration results from a A to G substitution at nucleotide position 1390, causing the isoleucine (I) at amino acid position 464 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.49

DANN

Benign

0.77

DEOGEN2

Benign

0.0072

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.76

M_CAP

Benign

0.013

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.28

REVEL

Benign

0.073

Sift4G

Benign

0.14

Polyphen

0.15

Vest4

0.087

MutPred

0.54

Loss of loop (P = 0.2237);

MVP

0.19

MPC

0.082

ClinPred

0.14

GERP RS

-0.079

Varity_R

0.12

gMVP

0.55

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