2-236214616-C-T

Variant names:

• chr2-236214616-C-T
• rs1015800358
• NM_212556.4:c.847G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_212556.4(ASB18):​c.847G>A​(p.Gly283Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000306 in 1,208,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: 6.61
• Publications: 2 publications found

Genes affected

ASB18 (HGNC:19770): (ankyrin repeat and SOCS box containing 18) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. [provided by RefSeq, Feb 2017]

GBX2-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212556.4. 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
	ASB18	NM_212556.4	MANE Select	c.847G>A	p.Gly283Arg	missense	Exon 4 of 6	NP_997721.2	Q6ZVZ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.847G>A	p.Gly283Arg	missense	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
	ASB18	ENST00000645891.1		c.760G>A	p.Gly254Arg	missense	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
	GBX2-AS1	ENST00000415226.1	TSL:4	n.224-44891C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000214 AC: 32 AN: 149216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000668

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: 0.000463

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 470 AF XY: 0.00

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: 0.000319 AC: 338 AN: 1059688 Hom.: 0 Cov.: 30 AF XY: 0.000337 AC XY: 170 AN XY: 504354

African (AFR) AF: 0.00 AC: 0 AN: 20980

American (AMR) AF: 0.000730 AC: 5 AN: 6854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12150

East Asian (EAS) AF: 0.00 AC: 0 AN: 21654

South Asian (SAS) AF: 0.0000401 AC: 1 AN: 24956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21220

Middle Eastern (MID) AF: 0.00112 AC: 3 AN: 2676

European-Non Finnish (NFE) AF: 0.000350 AC: 318 AN: 908068

Other (OTH) AF: 0.000267 AC: 11 AN: 41130

GnomAD4 genome AF: 0.000214 AC: 32 AN: 149216 Hom.: 0 Cov.: 32 AF XY: 0.000220 AC XY: 16 AN XY: 72738

African (AFR) AF: 0.00 AC: 0 AN: 41122

American (AMR) AF: 0.0000668 AC: 1 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9462

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

European-Non Finnish (NFE) AF: 0.000463 AC: 31 AN: 66962

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000261

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.0083	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.6
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.43		Gain of MoRF binding (P = 0.044)
MVP		0.72
MPC		1.8
ClinPred		0.99	D
GERP RS		3.7
PromoterAI		0.019	Neutral
Varity_R		0.38
gMVP		0.42
Mutation Taster		=62/38	polymorphism

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: rs1015800358; hg19: chr2-237123259; COSMIC: COSV58236162; COSMIC: COSV58236162;