2-232480086-T-C

Variant names:

• chr2-232480086-T-C
• rs114966878
• NM_004826.4:c.*67A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004826.4(ECEL1):​c.*67A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ECEL1 NM_004826.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 0 publications found

Genes affected

ECEL1 (HGNC:3147): (endothelin converting enzyme like 1) This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ECEL1 Gene-Disease associations (from GenCC):

• distal arthrogryposis type 5D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004826.4. 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
	ECEL1	NM_004826.4	MANE Select	c.*67A>G		3_prime_UTR	Exon 18 of 18	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.*67A>G		3_prime_UTR	Exon 18 of 18	NP_001277716.1	O95672-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECEL1	ENST00000304546.6	TSL:1 MANE Select	c.*67A>G		3_prime_UTR	Exon 18 of 18	ENSP00000302051.1	O95672-1
	ECEL1	ENST00000862796.1		c.*67A>G		3_prime_UTR	Exon 18 of 18	ENSP00000532855.1
	ECEL1	ENST00000931992.1		c.*67A>G		3_prime_UTR	Exon 18 of 18	ENSP00000602051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1358282 Hom.: 0 Cov.: 24 AF XY: 0.00000147 AC XY: 1 AN XY: 678100

African (AFR) AF: 0.00 AC: 0 AN: 31318

American (AMR) AF: 0.00 AC: 0 AN: 43004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23550

East Asian (EAS) AF: 0.00 AC: 0 AN: 38356

South Asian (SAS) AF: 0.00 AC: 0 AN: 81326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4886

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1028528

Other (OTH) AF: 0.00 AC: 0 AN: 56258

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs114966878; hg19: chr2-233344796;