rs1775437483

Variant names:

• chr6-117310261-C-A
• rs1775437483
• NM_001378902.1:c.6236G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-117310261-C-A
• chr6-117310261-C-G
• chr6-117310261-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001378902.1(ROS1):​c.6236G>T​(p.Cys2079Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: ROS1 NM_001378902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

Genes affected

ROS1 (HGNC:10261): (ROS proto-oncogene 1, receptor tyrosine kinase) This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.6236G>T	p.Cys2079Phe	missense_variant	Exon 41 of 44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.6236G>T	p.Cys2079Phe	missense_variant	Exon 41 of 44	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.6254G>T	p.Cys2085Phe	missense_variant	Exon 40 of 43	1		ENSP00000357494.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.0	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-10	D;D
REVEL	Pathogenic	0.88
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.86
MutPred		0.82		Loss of catalytic residue at L2086 (P = 0.0223);.;
MVP		0.68
MPC		0.24
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.99
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1775437483; hg19: chr6-117631424;