chr6-57183660-C-T

Variant names:

• chr6-57183660-C-T
• rs9885757
• NM_004282.4:c.224-118C>T

Variant summary

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

The NM_004282.4(BAG2):​c.224-118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 821,040 control chromosomes in the GnomAD database, including 25,816 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 0.29 (7369 hom., cov: 33)
  • Exomes 𝑓: 0.23 (18447 hom.)
• Consequence: BAG2 NM_004282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

BAG2 (HGNC:938): (BAG cochaperone 2) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAG2	NM_004282.4	c.224-118C>T		intron_variant	Intron 2 of 2	ENST00000370693.5	NP_004273.1
BAG2	XM_005249490.5	c.125-118C>T		intron_variant	Intron 3 of 3		XP_005249547.1
BAG2	XM_011514999.4	c.125-118C>T		intron_variant	Intron 3 of 3		XP_011513301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG2	ENST00000370693.5	c.224-118C>T		intron_variant	Intron 2 of 2	1	NM_004282.4	ENSP00000359727.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44202 AN: 151902 Hom.: 7353 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.226 AC: 151368 AN: 669020 Hom.: 18447 AF XY: 0.222 AC XY: 75199 AN XY: 338694

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.291 AC: 44264 AN: 152020 Hom.: 7369 Cov.: 33 AF XY: 0.290 AC XY: 21525 AN XY: 74276

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.269

Alfa AF: 0.274 Hom.: 938

Bravo AF: 0.292

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.32

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: rs9885757; hg19: chr6-57048458;