rs619203

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001378902.1(ROS1):​c.6668C>T​(p.Ser2223Phe) 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. 16/21 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: 32)

Consequence

ROS1
NM_001378902.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057365984).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ROS1NM_001378902.1 linkuse as main transcriptc.6668C>T p.Ser2223Phe missense_variant 43/44 ENST00000368507.8 NP_001365831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ROS1ENST00000368507.8 linkuse as main transcriptc.6668C>T p.Ser2223Phe missense_variant 43/445 NM_001378902.1 ENSP00000357493 P1
ROS1ENST00000368508.7 linkuse as main transcriptc.6686C>T p.Ser2229Phe missense_variant 42/431 ENSP00000357494

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
6.8
DANN
Benign
0.80
DEOGEN2
Benign
0.094
T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.29
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.057
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.32
N;N
REVEL
Benign
0.15
Sift
Benign
0.38
T;T
Sift4G
Benign
0.25
T;T
Polyphen
0.0
B;.
Vest4
0.14
MutPred
0.36
Loss of disorder (P = 0.0179);.;
MVP
0.17
MPC
0.026
ClinPred
0.11
T
GERP RS
2.2
Varity_R
0.087
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: chr6-117622184; API