7-32869547-T-C

Position:

• chr7-32869547-T-C

Variant summary

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

The NM_015483.3(KBTBD2):​c.1670A>G​(p.Glu557Gly) 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. 13/21 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)
• Consequence: KBTBD2 NM_015483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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=0.40625834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD2	NM_015483.3	c.1670A>G	p.Glu557Gly	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.1670A>G	p.Glu557Gly	missense_variant	4/4	1	NM_015483.3	ENSP00000302586.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Aug 02, 2023

The c.1670A>G (p.E557G) alteration is located in exon 4 (coding exon 3) of the KBTBD2 gene. This alteration results from a A to G substitution at nucleotide position 1670, causing the glutamic acid (E) at amino acid position 557 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Benign	0.21	T
Sift4G	Benign	0.093	T
Polyphen		0.034	B
Vest4		0.60
MutPred		0.41		Loss of solvent accessibility (P = 0.0477);
MVP		0.47
MPC		0.68
ClinPred		0.73	D
GERP RS		5.6
Varity_R		0.24
gMVP		0.55

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: chr7-32909159;