2-68979957-G-C

Variant names:

• chr2-68979957-G-C
• rs981209046
• NM_019617.4:c.360G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019617.4(GKN1):​c.360G>C​(p.Met120Ile) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GKN1 NM_019617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.412
• Publications: 0 publications found

Genes affected

GKN1 (HGNC:23217): (gastrokine 1) The protein encoded by this gene is found to be down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12682989).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GKN1	NM_019617.4	MANE Select	c.360G>C	p.Met120Ile	missense	Exon 5 of 6	NP_062563.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GKN1	ENST00000377938.4	TSL:1 MANE Select	c.360G>C	p.Met120Ile	missense	Exon 5 of 6	ENSP00000367172.3	Q9NS71
	GKN1	ENST00000673932.3		c.402G>C	p.Met134Ile	missense	Exon 5 of 6	ENSP00000501093.2	A0A8I5KHR1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.1
DANN	Benign	0.81
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.98	L
PhyloP100		-0.41
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.16
Sift	Benign	0.45	T
Sift4G	Benign	0.66	T
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.61		Loss of disorder (P = 0.0676)
MVP		0.76
MPC		0.19
ClinPred		0.027	T
GERP RS		-0.95
Varity_R		0.10
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs981209046; hg19: chr2-69207089;