chr2-232480452-C-A

Variant names:

• chr2-232480452-C-A
• rs199696717
• NM_004826.4:c.2175G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004826.4(ECEL1):​c.2175G>T​(p.Ser725Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,554 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: 0.0000021 (0 hom.)
• Consequence: ECEL1 NM_004826.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.2175G>T	p.Ser725Ser	synonymous_variant	Exon 17 of 18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.2169G>T	p.Ser723Ser	synonymous_variant	Exon 17 of 18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.2175G>T	p.Ser725Ser	synonymous_variant	Exon 17 of 18	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1	c.2169G>T	p.Ser723Ser	synonymous_variant	Exon 16 of 17	1		ENSP00000386333.1
ECEL1	ENST00000411860.5	c.354G>T	p.Ser118Ser	synonymous_variant	Exon 5 of 6	3		ENSP00000412683.1
ECEL1	ENST00000482346.1	n.2486G>T		non_coding_transcript_exon_variant	Exon 16 of 17	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250986 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135756

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461554 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000251 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: -19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199696717; hg19: chr2-233345162;