11-34152496-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145804.3(ABTB2):c.2969A>C(p.Gln990Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABTB2 NM_145804.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

Genes affected

ABTB2 (HGNC:23842): (ankyrin repeat and BTB domain containing 2) Predicted to enable protein heterodimerization activity. Predicted to act upstream of or within cellular response to toxic substance. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB2	NM_145804.3	c.2969A>C	p.Gln990Pro	missense_variant	17/17	ENST00000435224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB2	ENST00000435224.3	c.2969A>C	p.Gln990Pro	missense_variant	17/17	1	NM_145804.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 27, 2023

The c.2969A>C (p.Q990P) alteration is located in exon 17 (coding exon 17) of the ABTB2 gene. This alteration results from a A to C substitution at nucleotide position 2969, causing the glutamine (Q) at amino acid position 990 to be replaced by a proline (P). 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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.96	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.023	D
Vest4		0.60
MVP		0.57
MPC		0.23
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.76
gMVP		0.74

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: chr11-34174043;