2-28067480-T-C

Variant names:

• chr2-28067480-T-C
• rs13414801
• NM_199191.3:c.570+21681T>C

Variant summary

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

The NM_199191.3(BABAM2):​c.570+21681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,002 control chromosomes in the GnomAD database, including 24,863 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 0.56 (24863 hom., cov: 32)
• Consequence: BABAM2 NM_199191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965
• Publications: 7 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM2	NM_199191.3	c.570+21681T>C		intron_variant	Intron 6 of 11	ENST00000379624.6	NP_954661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM2	ENST00000379624.6	c.570+21681T>C		intron_variant	Intron 6 of 11	1	NM_199191.3	ENSP00000368945.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84657 AN: 151884 Hom.: 24862 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.557 AC: 84678 AN: 152002 Hom.: 24863 Cov.: 32 AF XY: 0.550 AC XY: 40891 AN XY: 74314

African (AFR) AF: 0.400 AC: 16575 AN: 41442

American (AMR) AF: 0.512 AC: 7808 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2032 AN: 5178

South Asian (SAS) AF: 0.701 AC: 3385 AN: 4826

European-Finnish (FIN) AF: 0.559 AC: 5894 AN: 10538

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44727 AN: 67974

Other (OTH) AF: 0.589 AC: 1241 AN: 2108

Alfa AF: 0.628 Hom.: 61276

Bravo AF: 0.540

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.96
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: rs13414801; hg19: chr2-28290347;