chr2-28065525-C-T

Position:

• chr2-28065525-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199191.3(BABAM2):​c.570+19726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,970 control chromosomes in the GnomAD database, including 20,466 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 0.51 (20466 hom., cov: 31)
• Consequence: BABAM2 NM_199191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM2	NM_199191.3	c.570+19726C>T		intron_variant		ENST00000379624.6	NP_954661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM2	ENST00000379624.6	c.570+19726C>T		intron_variant		1	NM_199191.3	ENSP00000368945	P1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77376 AN: 151850 Hom.: 20460 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.509 AC: 77400 AN: 151970 Hom.: 20466 Cov.: 31 AF XY: 0.500 AC XY: 37160 AN XY: 74286

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.499

Alfa AF: 0.568 Hom.: 33095

Bravo AF: 0.496

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs10173528; hg19: chr2-28288392;