18-46334301-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001256758.1(ARK2C):​c.-126C>G 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 0.00148 in 1,583,126 control chromosomes in the GnomAD database, including 13 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 0.0037 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (8 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BS2: High Homozygotes in GnomAd4 at 5 gene

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>G	p.Leu9Leu	synonymous	Exon 1 of 8	NP_689683.2	Q6ZSG1-1
	ARK2C	NM_001256758.1		c.-126C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001243687.1	Q6ZSG1-2
	ARK2C	NM_001256758.1		c.-126C>G		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>G	p.Leu9Leu	synonymous	Exon 1 of 8	ENSP00000269439.6	Q6ZSG1-1
	ARK2C	ENST00000543885.2	TSL:2	c.-126C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000444285.1	Q6ZSG1-2
	ARK2C	ENST00000956349.1		c.27C>G	p.Leu9Leu	synonymous	Exon 1 of 7	ENSP00000626408.1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 568 AN: 151490 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000825

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.00240 AC: 526 AN: 218806 AF XY: 0.00215

Gnomad AFR exome AF: 0.00875

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000636

Gnomad OTH exome AF: 0.00556

GnomAD4 exome AF: 0.00124 AC: 1779 AN: 1431540 Hom.: 8 Cov.: 32 AF XY: 0.00125 AC XY: 892 AN XY: 712416

African (AFR) AF: 0.00948 AC: 283 AN: 29838

American (AMR) AF: 0.00369 AC: 155 AN: 41996

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 581 AN: 25138

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

South Asian (SAS) AF: 0.000685 AC: 57 AN: 83268

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

Middle Eastern (MID) AF: 0.00433 AC: 23 AN: 5306

European-Non Finnish (NFE) AF: 0.000438 AC: 482 AN: 1101176

Other (OTH) AF: 0.00336 AC: 198 AN: 58974

GnomAD4 genome AF: 0.00373 AC: 566 AN: 151586 Hom.: 5 Cov.: 32 AF XY: 0.00377 AC XY: 279 AN XY: 74076

African (AFR) AF: 0.00858 AC: 356 AN: 41480

American (AMR) AF: 0.00315 AC: 48 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000825 AC: 56 AN: 67846

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00279 Hom.: 2

Bravo AF: 0.00408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.35
PromoterAI		0.030	Neutral
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;