rs370920665

chr12-25227260-T-Achr12-25227260-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_004985.5(KRAS):c.264A>T(p.Lys88Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K88K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRAS NM_004985.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a chain GTPase KRas (size 185) in uniprot entity RASK_HUMAN there are 119 pathogenic changes around while only 1 benign (99%) in NM_004985.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRAS	NM_033360.4	c.264A>T	p.Lys88Asn	missense_variant	3/6	ENST00000256078.10
KRAS	NM_004985.5	c.264A>T	p.Lys88Asn	missense_variant	3/5	ENST00000311936.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRAS	ENST00000256078.10	c.264A>T	p.Lys88Asn	missense_variant	3/6	1	NM_033360.4	A1
KRAS	ENST00000311936.8	c.264A>T	p.Lys88Asn	missense_variant	3/5	1	NM_004985.5	P4

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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.24	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.26
Sift	Benign	0.063	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.025	B;B
Vest4		0.80
MutPred		0.37		Gain of catalytic residue at N85 (P = 0.0054);Gain of catalytic residue at N85 (P = 0.0054);
MVP		0.69
MPC		2.1
ClinPred		0.72	D
GERP RS		-4.2
Varity_R		0.81
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-25380194;