7-32870004-C-G

Position:

• chr7-32870004-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000304056.9(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 ENST00000304056.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3796847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD2	NM_015483.3	c.1213G>C	p.Glu405Gln	missense_variant	4/4	ENST00000304056.9	NP_056298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD2	ENST00000304056.9	c.1213G>C	p.Glu405Gln	missense_variant	4/4	1	NM_015483.3	ENSP00000302586	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.1213G>C (p.E405Q) alteration is located in exon 4 (coding exon 3) of the KBTBD2 gene. This alteration results from a G to C substitution at nucleotide position 1213, causing the glutamic acid (E) at amino acid position 405 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D;D
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-32909616;