2-236195035-G-A

Variant names:

• chr2-236195035-G-A
• rs773073926
• NM_212556.4:c.1238C>T

Variant summary

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

The NM_212556.4(ASB18):​c.1238C>T​(p.Ser413Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,440 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89
• Publications: 0 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 2 ACMG points.

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

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.1238C>T	p.Ser413Phe	missense	Exon 6 of 6	NP_997721.2	Q6ZVZ8-1
	GBX2-AS1	NR_186035.1		n.229-18628G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.1238C>T	p.Ser413Phe	missense	Exon 6 of 6	ENSP00000386532.3	Q6ZVZ8-1
	ASB18	ENST00000645891.1		c.1151C>T	p.Ser384Phe	missense	Exon 5 of 5	ENSP00000496134.1	Q6ZVZ8-2
	GBX2-AS1	ENST00000415226.1	TSL:4	n.223+27366G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460440 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726440

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111328

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		6.9
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.93	P
Vest4		0.74
MVP		0.52
MPC		0.46
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.58
gMVP		0.47
Mutation Taster		=73/27	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: rs773073926; hg19: chr2-237103678;