2-28294994-A-G

Variant names:

• chr2-28294994-A-G
• rs4666051
• NM_199191.3:c.935-3344A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199191.3(BABAM2):​c.935-3344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,008 control chromosomes in the GnomAD database, including 33,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33816 hom., cov: 32)
• Consequence: BABAM2 NM_199191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM2	NM_199191.3	c.935-3344A>G		intron_variant	Intron 10 of 11	ENST00000379624.6	NP_954661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM2	ENST00000379624.6	c.935-3344A>G		intron_variant	Intron 10 of 11	1	NM_199191.3	ENSP00000368945.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100818 AN: 151890 Hom.: 33778 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 100914 AN: 152008 Hom.: 33816 Cov.: 32 AF XY: 0.665 AC XY: 49411 AN XY: 74304

African (AFR) AF: 0.735 AC: 30463 AN: 41452

American (AMR) AF: 0.716 AC: 10943 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3279 AN: 5160

South Asian (SAS) AF: 0.690 AC: 3322 AN: 4814

European-Finnish (FIN) AF: 0.591 AC: 6229 AN: 10546

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42151 AN: 67974

Other (OTH) AF: 0.709 AC: 1494 AN: 2108

Alfa AF: 0.662 Hom.: 4761

Bravo AF: 0.676

Asia WGS AF: 0.678 AC: 2358 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.54
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs4666051; hg19: chr2-28517861;