rs1555738370

Variant names:

• chr19-1220603-A-C
• rs1555738370
• NM_000455.5:c.620A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-1220603-A-C
• chr19-1220603-A-G
• chr19-1220603-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000455.5(STK11):​c.620A>C​(p.Asp207Ala) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D207E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.36
• Publications: 0 publications found

Genes affected

STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]

STK11 Gene-Disease associations (from GenCC):

• familial pancreatic carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Peutz-Jeghers syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.620A>C	p.Asp207Ala	missense	Exon 5 of 10	NP_000446.1
	STK11	NM_001407255.1		c.620A>C	p.Asp207Ala	missense	Exon 5 of 9	NP_001394184.1
	STK11	NR_176325.1		n.1887A>C		non_coding_transcript_exon	Exon 6 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.620A>C	p.Asp207Ala	missense	Exon 5 of 10	ENSP00000324856.6
	STK11	ENST00000652231.1		c.620A>C	p.Asp207Ala	missense	Exon 5 of 9	ENSP00000498804.1
	STK11	ENST00000585748.3	TSL:3	c.248A>C	p.Asp83Ala	missense	Exon 7 of 12	ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.085	T
Polyphen		0.52	P
Vest4		0.71
MutPred		0.56		Gain of catalytic residue at D207 (P = 0.0747)
MVP		0.69
MPC		1.6
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.65
gMVP		0.86
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs1555738370; hg19: chr19-1220602;