X-44232527-T-A

Position:

• chrX-44232527-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025184.4(EFHC2):​c.1574A>T​(p.Asn525Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,066,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: EFHC2 NM_025184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHC2	NM_025184.4	c.1574A>T	p.Asn525Ile	missense_variant	10/15	ENST00000420999.2	NP_079460.2
EFHC2	XM_047442535.1	c.1574A>T	p.Asn525Ile	missense_variant	10/14		XP_047298491.1
EFHC2	XM_047442536.1	c.1574A>T	p.Asn525Ile	missense_variant	10/15		XP_047298492.1
EFHC2	XM_006724562.3	c.986A>T	p.Asn329Ile	missense_variant	9/14		XP_006724625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHC2	ENST00000420999.2	c.1574A>T	p.Asn525Ile	missense_variant	10/15	1	NM_025184.4	ENSP00000404232.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1066898 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 341374

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: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Feb 07, 2024

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.43	T
REVEL	Uncertain	0.43
Sift4G	Uncertain	0.0030	D
Polyphen		0.90	P
Vest4		0.56
MutPred		0.68		Gain of sheet (P = 0.0827);
MVP		0.34
MPC		0.33
ClinPred		0.97	D
GERP RS		2.2
Varity_R		0.68
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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.

Other links and lift over

hg19: chrX-44091773;