18-46334301-C-T

Variant names:

• chr18-46334301-C-T
• rs79121450
• NM_152470.3:c.27C>T

Variant summary

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

The NM_001256758.1(ARK2C):​c.-126C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,583,046 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (1 hom.)
• Consequence: ARK2C NM_001256758.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 2 publications found

Genes affected

ARK2C (HGNC:31696): (arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in motor neuron axon guidance and positive regulation of BMP signaling pathway. Predicted to act upstream of or within several processes, including forelimb morphogenesis; multicellular organism aging; and nervous system development. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299713 (HGNC:):

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=-0.33).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256758.1. 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
	ARK2C	NM_152470.3	MANE Select	c.27C>T	p.Leu9Leu	synonymous	Exon 1 of 8	NP_689683.2	Q6ZSG1-1
	ARK2C	NM_001256758.1		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001243687.1	Q6ZSG1-2
	ARK2C	NM_001256758.1		c.-126C>T		5_prime_UTR	Exon 1 of 6	NP_001243687.1	Q6ZSG1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARK2C	ENST00000269439.12	TSL:2 MANE Select	c.27C>T	p.Leu9Leu	synonymous	Exon 1 of 8	ENSP00000269439.6	Q6ZSG1-1
	ARK2C	ENST00000543885.2	TSL:2	c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000444285.1	Q6ZSG1-2
	ARK2C	ENST00000956349.1		c.27C>T	p.Leu9Leu	synonymous	Exon 1 of 7	ENSP00000626408.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151492 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000457 AC: 1 AN: 218806 AF XY: 0.00000832

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1431554 Hom.: 1 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 712426

African (AFR) AF: 0.00 AC: 0 AN: 29840

American (AMR) AF: 0.00 AC: 0 AN: 41998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 36276

South Asian (SAS) AF: 0.0000600 AC: 5 AN: 83268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5306

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1101182

Other (OTH) AF: 0.00 AC: 0 AN: 58974

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151492 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73972

African (AFR) AF: 0.0000242 AC: 1 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67856

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		0.35
PromoterAI		0.025	Neutral

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: rs79121450; hg19: chr18-43914264; COSMIC: COSV53972148;