Variant 1-15410102-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024329.6(EFHD2):c.131C>T(p.Ala44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,471,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

EFHD2
NM_024329.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.340

Variant links:

Genes affected

EFHD2 (HGNC:28670): (EF-hand domain family member D2) Enables cadherin binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFHD2 links:

EFHD2-AS1 (HGNC:):

EFHD2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031787187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFHD2	NM_024329.6 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	1/4	ENST00000375980.9
EFHD2-AS1	NR_183705.1 linkuse as main transcript	n.463+1804G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFHD2	ENST00000375980.9 linkuse as main transcript	c.131C>T	p.Ala44Val	missense_variant	1/4	1	NM_024329.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

91210

Hom.:

AF XY:

0.0000376

AC XY:

AN XY:

53214

show subpopulations

Gnomad AFR exome

AF:

0.000693

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000682

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1319438

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

652020

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000432

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.54e-7

Gnomad4 OTH exome

AF:

0.000148

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151770

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ExAC

AF:

0.00000912

AC:

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

Feb 11, 2022

The c.131C>T (p.A44V) alteration is located in exon 1 (coding exon 1) of the EFHD2 gene. This alteration results from a C to T substitution at nucleotide position 131, causing the alanine (A) at amino acid position 44 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

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.73

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.54

REVEL

Benign

0.037

Sift

Benign

0.068

Sift4G

Benign

0.27

Polyphen

0.024

Vest4

0.14

MutPred

0.21

Gain of helix (P = 0.0143);

MVP

0.58

MPC

0.74

ClinPred

0.030

GERP RS

-0.085

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.061

gMVP

0.33

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