chr1-52896573-C-G

Variant names:

• chr1-52896573-C-G
• rs758715179
• NM_001198961.2:c.826G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001198961.2(ECHDC2):​c.826G>C​(p.Glu276Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECHDC2 NM_001198961.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80

Genes affected

ECHDC2 (HGNC:23408): (enoyl-CoA hydratase domain containing 2) Predicted to enable enoyl-CoA hydratase activity. Predicted to be involved in fatty acid beta-oxidation. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECHDC2	NM_001198961.2	c.826G>C	p.Glu276Gln	missense_variant	Exon 10 of 10	ENST00000371522.9	NP_001185890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECHDC2	ENST00000371522.9	c.826G>C	p.Glu276Gln	missense_variant	Exon 10 of 10	1	NM_001198961.2	ENSP00000360577.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.826G>C (p.E276Q) alteration is located in exon 10 (coding exon 10) of the ECHDC2 gene. This alteration results from a G to C substitution at nucleotide position 826, causing the glutamic acid (E) at amino acid position 276 to be replaced by a glutamine (Q). 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	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Pathogenic	3.7	.;H;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.68
MutPred		0.76		.;Gain of MoRF binding (P = 0.0237);.;
MVP		0.90
MPC		0.77
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.80

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

Other links and lift over

dbSNP: rs758715179; hg19: chr1-53362245; COSMIC: COSV64300247; COSMIC: COSV64300247;