dbSNP rs9885757: BAG2:c.224-118C>T (chr6-57183660-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

3 publications found

Variant links:

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]

BAG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
BAG2	NM_004282.4 link	c.224-118C>T	intron_variant	Intron 2 of 2	ENST00000370693.5	NP_004273.1	O95816-1
BAG2	XM_005249490.5 link	c.125-118C>T	intron_variant	Intron 3 of 3		XP_005249547.1	O95816-2
BAG2	XM_011514999.4 link	c.125-118C>T	intron_variant	Intron 3 of 3		XP_011513301.1	O95816-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAG2	ENST00000370693.5 link	c.224-118C>T		intron_variant	Intron 2 of 2	1	NM_004282.4	ENSP00000359727.4		O95816-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44202

AN:

151902

Hom.:

7353

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.462

AC:

7600

AN:

16434

American (AMR)

AF:

0.218

AC:

3420

AN:

15658

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

3363

AN:

14416

East Asian (EAS)

AF:

0.113

AC:

3566

AN:

31500

South Asian (SAS)

AF:

0.129

AC:

4905

AN:

37952

European-Finnish (FIN)

AF:

0.331

AC:

12598

AN:

38054

Middle Eastern (MID)

AF:

0.248

AC:

891

AN:

3590

European-Non Finnish (NFE)

AF:

0.224

AC:

107189

AN:

478748

Other (OTH)

AF:

0.240

AC:

7836

AN:

32668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5871

11743

17614

23486

29357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2688

5376

8064

10752

13440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.291

AC:

44264

AN:

152020

Hom.:

7369

Cov.:

AF XY:

0.290

AC XY:

21525

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.453

AC:

18788

AN:

41434

American (AMR)

AF:

0.215

AC:

3288

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

836

AN:

3464

East Asian (EAS)

AF:

0.139

AC:

720

AN:

5184

South Asian (SAS)

AF:

0.125

AC:

603

AN:

4814

European-Finnish (FIN)

AF:

0.353

AC:

3725

AN:

10544

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15432

AN:

67986

Other (OTH)

AF:

0.269

AC:

566

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1555

3110

4665

6220

7775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.32

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over