rs528903527

Variant names:

• chr2-28045744-G-A
• rs528903527
• NM_199191.3:c.515G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_199191.3(BABAM2):​c.515G>A​(p.Arg172His) variant causes a missense change. The variant allele was found at a frequency of 0.000041 in 1,610,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: BABAM2 NM_199191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35364115).

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.515G>A	p.Arg172His	missense	Exon 6 of 12	NP_954661.1	Q9NXR7-2
	BABAM2	NM_001329114.2		c.515G>A	p.Arg172His	missense	Exon 6 of 14	NP_001316043.1
	BABAM2	NM_001329115.2		c.515G>A	p.Arg172His	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.515G>A	p.Arg172His	missense	Exon 6 of 12	ENSP00000368945.1	Q9NXR7-2
	BABAM2	ENST00000342045.6	TSL:1	c.515G>A	p.Arg172His	missense	Exon 7 of 13	ENSP00000339371.2	Q9NXR7-2
	BABAM2	ENST00000361704.6	TSL:1	c.515G>A	p.Arg172His	missense	Exon 6 of 13	ENSP00000354699.2	Q9NXR7-4

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152024 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 250740 AF XY: 0.0000590

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000377 AC: 55 AN: 1458514 Hom.: 0 Cov.: 30 AF XY: 0.0000427 AC XY: 31 AN XY: 725512

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39592

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1109854

Other (OTH) AF: 0.0000997 AC: 6 AN: 60206

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152142 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74378

African (AFR) AF: 0.0000723 AC: 3 AN: 41484

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000741 AC: 9

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	0.25
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.27	T
PhyloP100		5.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.60
MVP		0.61
MPC		0.84
ClinPred		0.24	T
GERP RS		5.4
Varity_R		0.37
gMVP		0.48
Mutation Taster		=69/31	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: rs528903527; hg19: chr2-28268611;