19-41242848-T-G

Variant names:

• chr19-41242848-T-G
• rs2304234
• NM_021913.5:c.1313-35T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021913.5(AXL):​c.1313-35T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AXL NM_021913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXL	NM_021913.5	c.1313-35T>G		intron_variant	Intron 10 of 19	ENST00000301178.9	NP_068713.2
AXL	NM_001699.6	c.1286-35T>G		intron_variant	Intron 9 of 18		NP_001690.2
AXL	NM_001278599.2	c.509-35T>G		intron_variant	Intron 7 of 16		NP_001265528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXL	ENST00000301178.9	c.1313-35T>G		intron_variant	Intron 10 of 19	1	NM_021913.5	ENSP00000301178.3
AXL	ENST00000359092.7	c.1286-35T>G		intron_variant	Intron 9 of 18	1		ENSP00000351995.2
AXL	ENST00000593513.1	c.509-35T>G		intron_variant	Intron 7 of 16	1		ENSP00000471497.1
AXL	ENST00000599659.5	n.1327-35T>G		intron_variant	Intron 10 of 11	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		-0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2304234; hg19: chr19-41748753;