2-68977644-A-C

Variant names:

• chr2-68977644-A-C
• NM_019617.4:c.74A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019617.4(GKN1):​c.74A>C​(p.Asn25Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GKN1 NM_019617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.260
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30355388).

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.74A>C	p.Asn25Thr	missense	Exon 3 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.74A>C	p.Asn25Thr	missense	Exon 3 of 6	ENSP00000367172.3	Q9NS71
	GKN1	ENST00000673932.3		c.116A>C	p.Asn39Thr	missense	Exon 3 of 6	ENSP00000501093.2	A0A8I5KHR1
	GKN1	ENST00000478888.1	TSL:2	n.116A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458626 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725912

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109112

Other (OTH) AF: 0.00 AC: 0 AN: 60276

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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.26
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.042
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.059	T
Polyphen		0.91	P
Vest4		0.36
MutPred		0.49		Gain of glycosylation at N39 (P = 0.0197)
MVP		0.48
MPC		0.47
ClinPred		0.87	D
GERP RS		1.6
Varity_R		0.15
gMVP		0.51
Mutation Taster		=94/6	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

hg19: chr2-69204776;