chr2-28045786-C-T

Variant names:

• chr2-28045786-C-T
• rs1677510948
• NM_199191.3:c.557C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199191.3(BABAM2):​c.557C>T​(p.Thr186Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BABAM2 NM_199191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23168996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199191.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM2	NM_199191.3	MANE Select	c.557C>T	p.Thr186Ile	missense	Exon 6 of 12	NP_954661.1	Q9NXR7-2
	BABAM2	NM_001329114.2		c.557C>T	p.Thr186Ile	missense	Exon 6 of 14	NP_001316043.1
	BABAM2	NM_001329115.2		c.557C>T	p.Thr186Ile	missense	Exon 7 of 14	NP_001316044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BABAM2	ENST00000379624.6	TSL:1 MANE Select	c.557C>T	p.Thr186Ile	missense	Exon 6 of 12	ENSP00000368945.1	Q9NXR7-2
	BABAM2	ENST00000342045.6	TSL:1	c.557C>T	p.Thr186Ile	missense	Exon 7 of 13	ENSP00000339371.2	Q9NXR7-2
	BABAM2	ENST00000361704.6	TSL:1	c.557C>T	p.Thr186Ile	missense	Exon 6 of 13	ENSP00000354699.2	Q9NXR7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455748 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724184

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.0000224 AC: 1 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 85172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108032

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Benign	0.49	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.53		Loss of helix (P = 0.028)
MVP		0.27
MPC		0.40
ClinPred		0.77	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.15
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1677510948; hg19: chr2-28268653;