2-236214580-T-G

Variant names:

• chr2-236214580-T-G
• NM_212556.4:c.883A>C
• ASB18 p.Ser295Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_212556.4(ASB18):​c.883A>C​(p.Ser295Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2796913).

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.883A>C	p.Ser295Arg	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.883A>C	p.Ser295Arg	missense	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
	ASB18	ENST00000645891.1		c.796A>C	p.Ser266Arg	missense	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
	ASB18	ENST00000447030.1	TSL:4	c.22A>C	p.Ser8Arg	missense	Exon 1 of 2	ENSP00000411434.1	H7C3E8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.22	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.53	T
Sift4G	Benign	0.42	T
PromoterAI		0.15	Neutral
Varity_R		0.30
gMVP		0.63
Mutation Taster		=70/30	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-237123223;