NM_001378902.1:c.7003G>C

Variant names:

• chr6-117288515-C-G
• NM_001378902.1:c.7003G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378902.1(ROS1):​c.7003G>C​(p.Gly2335Arg) variant causes a missense 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. 14/21 in silico tools predict 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: 33)
• Consequence: ROS1 NM_001378902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1776425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.7003G>C	p.Gly2335Arg	missense_variant	Exon 44 of 44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.7003G>C	p.Gly2335Arg	missense_variant	Exon 44 of 44	5	NM_001378902.1	ENSP00000357493.3
ROS1	ENST00000368508.7	c.7021G>C	p.Gly2341Arg	missense_variant	Exon 43 of 43	1		ENSP00000357494.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.0079
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.079
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.62	P;.
Vest4		0.36
MutPred		0.15		Loss of glycosylation at S2340 (P = 0.0846);.;
MVP		0.51
MPC		0.14
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.15
gMVP		0.31

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: chr6-117609678;