rs147677701

Variant names:

• chr1-52896578-C-G
• rs147677701
• NM_001198961.2:c.821G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-52896578-C-G
• chr1-52896578-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001198961.2(ECHDC2):​c.821G>C​(p.Arg274Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R274Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECHDC2 NM_001198961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198961.2. 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
	ECHDC2	NM_001198961.2	MANE Select	c.821G>C	p.Arg274Pro	missense	Exon 10 of 10	NP_001185890.1	Q86YB7-1
	ECHDC2	NM_018281.4		c.728G>C	p.Arg243Pro	missense	Exon 9 of 9	NP_060751.2	Q86YB7-2
	ECHDC2	NM_001198962.1		c.677G>C	p.Arg226Pro	missense	Exon 8 of 8	NP_001185891.1	F6RJU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECHDC2	ENST00000371522.9	TSL:1 MANE Select	c.821G>C	p.Arg274Pro	missense	Exon 10 of 10	ENSP00000360577.4	Q86YB7-1
	ECHDC2	ENST00000371520.5	TSL:1	n.*1032G>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000360575.1	F5H0R2
	ECHDC2	ENST00000371520.5	TSL:1	n.*1032G>C		3_prime_UTR	Exon 10 of 10	ENSP00000360575.1	F5H0R2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.65		Loss of MoRF binding (P = 0.0202)
MVP		0.91
MPC		0.94
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.97
gMVP		0.96
Mutation Taster		=15/85	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147677701; hg19: chr1-53362250;