1-52899212-C-A

Variant names:

• chr1-52899212-C-A
• rs374095939
• NM_001198961.2:c.715G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001198961.2(ECHDC2):​c.715G>T​(p.Val239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V239M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECHDC2 NM_001198961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 2 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 2 ACMG points.

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

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.715G>T	p.Val239Leu	missense	Exon 8 of 10	NP_001185890.1	Q86YB7-1
	ECHDC2	NM_018281.4		c.622G>T	p.Val208Leu	missense	Exon 7 of 9	NP_060751.2	Q86YB7-2
	ECHDC2	NM_001319958.2		c.484G>T	p.Val162Leu	missense	Exon 8 of 10	NP_001306887.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECHDC2	ENST00000371522.9	TSL:1 MANE Select	c.715G>T	p.Val239Leu	missense	Exon 8 of 10	ENSP00000360577.4	Q86YB7-1
	ECHDC2	ENST00000371520.5	TSL:1	n.*926G>T		non_coding_transcript_exon	Exon 8 of 10	ENSP00000360575.1	F5H0R2
	ECHDC2	ENST00000371520.5	TSL:1	n.*926G>T		3_prime_UTR	Exon 8 of 10	ENSP00000360575.1	F5H0R2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.050	N
PhyloP100		1.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Benign	0.24	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.52
MutPred		0.53		Loss of MoRF binding (P = 0.1161)
MVP		0.60
MPC		0.40
ClinPred		0.86	D
GERP RS		5.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.36
gMVP		0.90
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs374095939; hg19: chr1-53364884;