Variant 12-25245295-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The ENST00000311936.8(KRAS):c.90C>A(p.Asp30Glu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. D30D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

KRAS
ENST00000311936.8 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

KRAS (HGNC:6407): (KRAS proto-oncogene, GTPase) This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]

KRAS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 8 uncertain in ENST00000311936.8

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25021857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRAS	NM_033360.4 linkuse as main transcript	c.90C>A	p.Asp30Glu	missense_variant	2/6	ENST00000256078.10	NP_203524.1
KRAS	NM_004985.5 linkuse as main transcript	c.90C>A	p.Asp30Glu	missense_variant	2/5	ENST00000311936.8	NP_004976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRAS	ENST00000256078.10 linkuse as main transcript	c.90C>A	p.Asp30Glu	missense_variant	2/6	1	NM_033360.4	ENSP00000256078	A1	P01116-1
KRAS	ENST00000311936.8 linkuse as main transcript	c.90C>A	p.Asp30Glu	missense_variant	2/5	1	NM_004985.5	ENSP00000308495	P4	P01116-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Prostate cancer, hereditary, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Laboratory of Virology, Oncology, Biosciences and Environment, Faculty of Sciences and Techniques, Mohammedia- University Hassan II of Casablanca

Jul 29, 2022

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

0.0080

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.55

.;.;D;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.96

N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.55

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;.;B;.

Vest4

0.69

MutPred

0.40

Gain of catalytic residue at E31 (P = 0.089);Gain of catalytic residue at E31 (P = 0.089);Gain of catalytic residue at E31 (P = 0.089);Gain of catalytic residue at E31 (P = 0.089);

MVP

0.46

MPC

1.4

ClinPred

0.11

GERP RS

-2.0

Varity_R

0.21

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over