rs7231421

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152470.3(ARK2C):​c.61+34245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,240 control chromosomes in the GnomAD database, including 1,770 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 0.11 ( 1770 hom., cov: 33)

Consequence

ARK2C
NM_152470.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARK2CNM_152470.3 linkuse as main transcriptc.61+34245C>T intron_variant ENST00000269439.12
ARK2CNM_001256758.1 linkuse as main transcriptc.-92+34245C>T intron_variant
ARK2CXM_011526016.4 linkuse as main transcriptc.61+34245C>T intron_variant
ARK2CXM_017025788.3 linkuse as main transcriptc.61+34245C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARK2CENST00000269439.12 linkuse as main transcriptc.61+34245C>T intron_variant 2 NM_152470.3 P1Q6ZSG1-1
ARK2CENST00000543885.2 linkuse as main transcriptc.-92+34245C>T intron_variant 2 Q6ZSG1-2
ARK2CENST00000593230.5 linkuse as main transcriptc.-141+41633C>T intron_variant 3
ARK2CENST00000586604.5 linkuse as main transcriptc.61+34245C>T intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.109
AC:
16623
AN:
152122
Hom.:
1762
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.275
Gnomad AMI
AF:
0.0110
Gnomad AMR
AF:
0.0593
Gnomad ASJ
AF:
0.0268
Gnomad EAS
AF:
0.0935
Gnomad SAS
AF:
0.0350
Gnomad FIN
AF:
0.0855
Gnomad MID
AF:
0.0759
Gnomad NFE
AF:
0.0364
Gnomad OTH
AF:
0.0832
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.109
AC:
16656
AN:
152240
Hom.:
1770
Cov.:
33
AF XY:
0.109
AC XY:
8103
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.275
Gnomad4 AMR
AF:
0.0591
Gnomad4 ASJ
AF:
0.0268
Gnomad4 EAS
AF:
0.0935
Gnomad4 SAS
AF:
0.0350
Gnomad4 FIN
AF:
0.0855
Gnomad4 NFE
AF:
0.0364
Gnomad4 OTH
AF:
0.0818
Alfa
AF:
0.0492
Hom.:
566
Bravo
AF:
0.117
Asia WGS
AF:
0.0790
AC:
276
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.2
DANN
Benign
0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7231421; hg19: chr18-43948543; API