19-41220698-CTC-GTT

Variant names:

• chr19-41220698-CTC-GTT
• NM_021913.5:c.148_150delCTCinsGTT
• AXL p.Leu50Val

Variant summary

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

The NM_021913.5(AXL):​c.148_150delCTCinsGTT​(p.Leu50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L50F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AXL NM_021913.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

AXL (HGNC:905): (AXL receptor tyrosine kinase) The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. The encoded protein acts as a host cell receptor for multiple viruses, including Marburg, Ebola and Lassa viruses and is a candidate receptor for the SARS-CoV2 virus. [provided by RefSeq, Sep 2021]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021913.5. 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
	AXL	NM_021913.5	MANE Select	c.148_150delCTCinsGTT	p.Leu50Val	missense	N/A	NP_068713.2
	AXL	NM_001699.6		c.148_150delCTCinsGTT	p.Leu50Val	missense	N/A	NP_001690.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXL	ENST00000301178.9	TSL:1 MANE Select	c.148_150delCTCinsGTT	p.Leu50Val	missense	N/A	ENSP00000301178.3	P30530-1
	AXL	ENST00000359092.7	TSL:1	c.148_150delCTCinsGTT	p.Leu50Val	missense	N/A	ENSP00000351995.2	P30530-2
	AXL	ENST00000599659.5	TSL:1	n.162_164delCTCinsGTT		non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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: chr19-41726603;