2-236214525-A-T

Variant names:

• chr2-236214525-A-T
• NM_212556.4:c.938T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_212556.4(ASB18):​c.938T>A​(p.Leu313Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L313R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB18 NM_212556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB18	NM_212556.4	c.938T>A	p.Leu313Gln	missense_variant	Exon 4 of 6	ENST00000409749.8	NP_997721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB18	ENST00000409749.8	c.938T>A	p.Leu313Gln	missense_variant	Exon 4 of 6	1	NM_212556.4	ENSP00000386532.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.938T>A (p.L313Q) alteration is located in exon 4 (coding exon 4) of the ASB18 gene. This alteration results from a T to A substitution at nucleotide position 938, causing the leucine (L) at amino acid position 313 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;T;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Pathogenic	3.5	.;M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.1	.;D;D
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.72
MutPred		0.75		.;Loss of stability (P = 0.0255);.;
MVP		0.84
MPC		2.3
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.77
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-237123168;