17-1010843-T-C

Position:

• chr17-1010843-T-C

Variant summary

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

The ENST00000302538.10(ABR):​c.2122A>G​(p.Met708Val) 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: 33)
• Consequence: ABR ENST00000302538.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

Genes affected

ABR (HGNC:81): (ABR activator of RhoGEF and GTPase) This gene encodes a protein that is similar to the protein encoded by the breakpoint cluster region gene located on chromosome 22. The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein plays a role in vestibular morphogenesis. Alternatively spliced transcript variants have been reported for this gene. [provided by RefSeq, Feb 2012]

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	Protein	UniProt
ABR	NM_021962.5	c.2122A>G	p.Met708Val	missense_variant	20/23	ENST00000302538.10	NP_068781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABR	ENST00000302538.10	c.2122A>G	p.Met708Val	missense_variant	20/23	1	NM_021962.5	ENSP00000303909	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 23, 2023

The c.2122A>G (p.M708V) alteration is located in exon 20 (coding exon 20) of the ABR gene. This alteration results from a A to G substitution at nucleotide position 2122, causing the methionine (M) at amino acid position 708 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T;.;.;.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	.;.;D;.;.;.
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.44	N;.;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.1	N;N;.;N;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D;.;D;T;D
Sift4G	Benign	0.16	T;T;.;T;T;T
Polyphen		0.24	B;.;.;B;.;B
Vest4		0.41
MutPred		0.51		Gain of catalytic residue at M708 (P = 0.0076);.;.;.;.;.;
MVP		0.83
MPC		1.1
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.58
gMVP		0.81

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: chr17-914083;