chr2-236195054-G-A

Variant names:

• chr2-236195054-G-A
• rs10177957
• NM_212556.4:c.1219C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_212556.4(ASB18):​c.1219C>T​(p.His407Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,607,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 15 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	NM_212556.4	MANE Select	c.1219C>T	p.His407Tyr	missense	Exon 6 of 6	NP_997721.2
	GBX2-AS1	NR_186035.1		n.229-18609G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.1219C>T	p.His407Tyr	missense	Exon 6 of 6	ENSP00000386532.3
	ASB18	ENST00000645891.1		c.1132C>T	p.His378Tyr	missense	Exon 5 of 5	ENSP00000496134.1
	GBX2-AS1	ENST00000415226.1	TSL:4	n.223+27385G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.00000815 AC: 2 AN: 245254 AF XY: 0.00

Gnomad AFR exome AF: 0.000132

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: 0.00000137 AC: 2 AN: 1454910 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722538

African (AFR) AF: 0.0000601 AC: 2 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 85598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107678

Other (OTH) AF: 0.00 AC: 0 AN: 60024

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.0000483 AC: 2 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 3002

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Benign	0.092	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.63		Loss of methylation at K408 (P = 0.1724)
MVP		0.34
MPC		0.39
ClinPred		0.89	D
GERP RS		3.7
Varity_R		0.12
gMVP		0.47
Mutation Taster		=91/9	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: rs10177957; hg19: chr2-237103697;