EFHC2 p.Glu747Asp

Variant names:

• chrX-44148804-C-A
• NM_025184.4:c.2241G>T
• EFHC2 p.Glu747Asp

Your query was ambiguous. Multiple possible variants found:

• chrX-44148804-C-A
• chrX-44148804-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025184.4(EFHC2):​c.2241G>T​(p.Glu747Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: EFHC2 NM_025184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043348223).

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.2241G>T	p.Glu747Asp	missense	Exon 15 of 15	NP_079460.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC2	ENST00000420999.2	TSL:1 MANE Select	c.2241G>T	p.Glu747Asp	missense	Exon 15 of 15	ENSP00000404232.2	Q5JST6-1
	EFHC2	ENST00000937700.1		c.2148G>T	p.Glu716Asp	missense	Exon 14 of 14	ENSP00000607759.1
	EFHC2	ENST00000889038.1		c.2115G>T	p.Glu705Asp	missense	Exon 15 of 15	ENSP00000559097.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1066306 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 345680

African (AFR) AF: 0.00 AC: 0 AN: 25674

American (AMR) AF: 0.00 AC: 0 AN: 30451

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18772

East Asian (EAS) AF: 0.00 AC: 0 AN: 28657

South Asian (SAS) AF: 0.00 AC: 0 AN: 49674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825276

Other (OTH) AF: 0.00 AC: 0 AN: 44960

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.074
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0064	T
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.59
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.085
Sift	Benign	0.36	T
Sift4G	Benign	0.12	T
Varity_R		0.11
gMVP		0.15
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-44008050;