7-32870057-C-T

Variant names:

• chr7-32870057-C-T
• NM_015483.3:c.1160G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015483.3(KBTBD2):​c.1160G>A​(p.Gly387Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KBTBD2 NM_015483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84
• Publications: 0 publications found

Genes affected

KBTBD2 (HGNC:21751): (kelch repeat and BTB domain containing 2) Predicted to act upstream of or within with a positive effect on several processes, including glucose metabolic process; phosphatidylinositol 3-kinase signaling; and response to insulin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015483.3. 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
	KBTBD2	NM_015483.3	MANE Select	c.1160G>A	p.Gly387Glu	missense	Exon 4 of 4	NP_056298.2	A0A024RA38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD2	ENST00000304056.9	TSL:1 MANE Select	c.1160G>A	p.Gly387Glu	missense	Exon 4 of 4	ENSP00000302586.4	Q8IY47
	KBTBD2	ENST00000896919.1		c.1160G>A	p.Gly387Glu	missense	Exon 5 of 5	ENSP00000566978.1
	KBTBD2	ENST00000896920.1		c.1160G>A	p.Gly387Glu	missense	Exon 5 of 5	ENSP00000566979.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.84	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.86	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		7.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.99
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.93		Gain of glycosylation at S389 (P = 0.1166)
MVP		0.98
MPC		1.7
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.74
gMVP		0.95
Mutation Taster		=21/79	disease causing

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: chr7-32909669;