NM_007314.4:c.43C>T

Variant names:

• chr1-179229355-G-A
• rs1553236156
• NM_007314.4:c.43C>T

Variant summary

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

The NM_007314.4(ABL2):​c.43C>T​(p.Gln15*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABL2 NM_007314.4 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

Genes affected

ABL2 (HGNC:77): (ABL proto-oncogene 2, non-receptor tyrosine kinase) This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

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_007314.4. 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
	ABL2	NM_007314.4	MANE Select	c.43C>T	p.Gln15*	stop_gained	Exon 1 of 12	NP_009298.1
	ABL2	NM_001168236.2		c.43C>T	p.Gln15*	stop_gained	Exon 1 of 11	NP_001161708.1
	ABL2	NM_001168237.2		c.43C>T	p.Gln15*	stop_gained	Exon 1 of 13	NP_001161709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABL2	ENST00000502732.6	TSL:1 MANE Select	c.43C>T	p.Gln15*	stop_gained	Exon 1 of 12	ENSP00000427562.1
	ABL2	ENST00000367623.8	TSL:1	c.43C>T	p.Gln15*	stop_gained	Exon 1 of 11	ENSP00000356595.4
	ABL2	ENST00000511413.5	TSL:1	c.43C>T	p.Gln15*	stop_gained	Exon 1 of 13	ENSP00000424697.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1424742 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 707436

African (AFR) AF: 0.00 AC: 0 AN: 30496

American (AMR) AF: 0.00 AC: 0 AN: 40270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24212

East Asian (EAS) AF: 0.00 AC: 0 AN: 36934

South Asian (SAS) AF: 0.00 AC: 0 AN: 82444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098012

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 08, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.27	N
PhyloP100		2.4
Vest4		0.60
GERP RS		4.0
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Mutation Taster		=1/199	disease causing (fs/PTC)

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: rs1553236156; hg19: chr1-179198490;