rs764578894

Variant names:

• chrX-44148819-G-A
• rs764578894
• NM_025184.4:c.2226C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-44148819-G-A
• chrX-44148819-G-C
• chrX-44148819-G-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_025184.4(EFHC2):​c.2226C>T​(p.Asp742Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,182,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000051 (0 hom. 24 hem.)
• Consequence: EFHC2 NM_025184.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.027).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 24 gene

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.2226C>T	p.Asp742Asp	synonymous	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.2226C>T	p.Asp742Asp	synonymous	Exon 15 of 15	ENSP00000404232.2
	EFHC2	ENST00000937700.1		c.2133C>T	p.Asp711Asp	synonymous	Exon 14 of 14	ENSP00000607759.1
	EFHC2	ENST00000889038.1		c.2100C>T	p.Asp700Asp	synonymous	Exon 15 of 15	ENSP00000559097.1

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111483 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000956

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

GnomAD2 exomes AF: 0.0000877 AC: 12 AN: 136761 AF XY: 0.000176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000914

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000971

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000514 AC: 55 AN: 1070559 Hom.: 0 Cov.: 29 AF XY: 0.0000691 AC XY: 24 AN XY: 347377

African (AFR) AF: 0.0000388 AC: 1 AN: 25797

American (AMR) AF: 0.0000640 AC: 2 AN: 31256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18818

East Asian (EAS) AF: 0.0000345 AC: 1 AN: 28954

South Asian (SAS) AF: 0.000419 AC: 21 AN: 50070

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 38987

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 0.0000326 AC: 27 AN: 827455

Other (OTH) AF: 0.0000443 AC: 2 AN: 45118

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111483 Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1 AN XY: 33719

African (AFR) AF: 0.00 AC: 0 AN: 30711

American (AMR) AF: 0.0000956 AC: 1 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 2649

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53108

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0060
DANN	Benign	0.19
PhyloP100		-1.1
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs764578894; hg19: chrX-44008065; COSMIC: COSV100637882;