chr2-236196314-C-G

Variant names:

• chr2-236196314-C-G
• NM_212556.4:c.1173G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_212556.4(ASB18):​c.1173G>C​(p.Leu391Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.324
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14326394).

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.1173G>C	p.Leu391Phe	missense	Exon 5 of 6	NP_997721.2	Q6ZVZ8-1
	GBX2-AS1	NR_186035.1		n.229-17349C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	ENST00000409749.8	TSL:1 MANE Select	c.1173G>C	p.Leu391Phe	missense	Exon 5 of 6	ENSP00000386532.3	Q6ZVZ8-1
	ASB18	ENST00000645891.1		c.1086G>C	p.Leu362Phe	missense	Exon 4 of 5	ENSP00000496134.1	Q6ZVZ8-2
	ASB18	ENST00000447030.1	TSL:4	c.312G>C	p.Leu104Phe	missense	Exon 2 of 2	ENSP00000411434.1	H7C3E8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412810 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698154

African (AFR) AF: 0.00 AC: 0 AN: 32188

American (AMR) AF: 0.00 AC: 0 AN: 37808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 36900

South Asian (SAS) AF: 0.00 AC: 0 AN: 80008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085928

Other (OTH) AF: 0.00 AC: 0 AN: 58626

GnomAD4 genome Cov.: 32

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	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.32
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.042
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		0.11	B
Vest4		0.071
MutPred		0.38		Loss of catalytic residue at L391 (P = 0.0317)
MVP		0.14
MPC		1.2
ClinPred		0.40	T
GERP RS		1.1
Varity_R		0.071
gMVP		0.28
Mutation Taster		=92/8	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

hg19: chr2-237104957;