chr1-52896584-C-G

Variant names:

• chr1-52896584-C-G
• rs536501241
• NM_001198961.2:c.815G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001198961.2(ECHDC2):​c.815G>C​(p.Arg272Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R272W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ECHDC2 NM_001198961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34668672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECHDC2	NM_001198961.2	c.815G>C	p.Arg272Pro	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.815G>C	p.Arg272Pro	missense_variant	Exon 10 of 10	1	NM_001198961.2	ENSP00000360577.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461740 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-0.30	.;N;.
PhyloP100		-0.40
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.0	.;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.98, 0.98	.;D;D
Vest4		0.34
MutPred		0.49		.;Loss of catalytic residue at R272 (P = 0.0197);.;
MVP		0.65
MPC		0.90
ClinPred		0.97	D
GERP RS		-1.5
Varity_R		0.78
gMVP		0.89
Mutation Taster		=64/36	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: rs536501241; hg19: chr1-53362256;