chr2-28244787-G-T

Position:

• chr2-28244787-G-T

Variant summary

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

The NM_199191.3(BABAM2):​c.859G>T​(p.Val287Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V287M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BABAM2 NM_199191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.04

Genes affected

BABAM2 (HGNC:1106): (BRISC and BRCA1 A complex member 2) This gene encodes an anti-apoptotic, death receptor-associated protein that interacts with tumor necrosis factor-receptor-1. The encoded protein acts as an adapter in several protein complexes, including the BRCA1-A complex and the BRISC complex. The BRCA1-A complex possesses ubiquitinase activity and targets sites of double strand DNA breaks, while the BRISC complex exhibits deubiquitinase activity and is involved in mitotic spindle assembly. This gene is upregulated in several types of cancer. [provided by RefSeq, Jun 2016]

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
BABAM2	NM_199191.3	c.859G>T	p.Val287Leu	missense_variant	10/12	ENST00000379624.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BABAM2	ENST00000379624.6	c.859G>T	p.Val287Leu	missense_variant	10/12	1	NM_199191.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Apr 15, 2024

The c.859G>T (p.V287L) alteration is located in exon 10 (coding exon 9) of the BRE gene. This alteration results from a G to T substitution at nucleotide position 859, causing the valine (V) at amino acid position 287 to be replaced by a leucine (L). 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	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	.;T;T;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;D;.;D
M_CAP	Benign	0.0054	T
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	1.1	N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.85	T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T
Polyphen		0.98	D;D;D;B;B
Vest4		0.85
MutPred		0.60		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.35
MPC		0.38
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.35
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr2-28467654;