Variant 6-117317181-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001378902.1(ROS1):c.6079G>A(p.Asp2027Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ROS1
NM_001378902.1 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.41

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]

ROS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1 linkuse as main transcript	c.6079G>A	p.Asp2027Asn	missense_variant	39/44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8 linkuse as main transcript	c.6079G>A	p.Asp2027Asn	missense_variant	39/44	5	NM_001378902.1	ENSP00000357493.3		Q5H8Y1
ROS1	ENST00000368508.7 linkuse as main transcript	c.6097G>A	p.Asp2033Asn	missense_variant	38/43	1		ENSP00000357494.3		P08922

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250934

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461130

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Lung sarcomatoid carcinoma

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Salgia Laboratory, City of Hope

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

1.0

D;.

Vest4

0.58

MutPred

0.81

Gain of catalytic residue at D2033 (P = 0.0255);.;

MVP

0.64

MPC

0.21

ClinPred

1.0

GERP RS

5.0

Varity_R

0.89

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over