chr7-32870004-C-G

Variant names:

• chr7-32870004-C-G
• NM_015483.3:c.1213G>C

Variant summary

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

The NM_015483.3(KBTBD2):​c.1213G>C​(p.Glu405Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 6.02
• 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: 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=0.3796847).

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.1213G>C	p.Glu405Gln	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.1213G>C	p.Glu405Gln	missense	Exon 4 of 4	ENSP00000302586.4	Q8IY47
	KBTBD2	ENST00000896919.1		c.1213G>C	p.Glu405Gln	missense	Exon 5 of 5	ENSP00000566978.1
	KBTBD2	ENST00000896920.1		c.1213G>C	p.Glu405Gln	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	Benign	0.085
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.99	L
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.13	N
REVEL	Uncertain	0.35
Sift	Benign	0.79	T
Sift4G	Benign	0.074	T
Polyphen		0.97	D
Vest4		0.45
MutPred		0.51		Loss of disorder (P = 0.0983)
MVP		0.78
MPC		1.2
ClinPred		0.73	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.36
Mutation Taster		=68/32	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: chr7-32909616;