Genetic Variant BAG2:c.113+761A>C (chr6-57173571-A-C) – 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.113+761A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 853,372 control chromosomes in the GnomAD database, including 2,792 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 0.089 ( 673 hom., cov: 32)

Exomes 𝑓: 0.076 ( 2119 hom. )

Consequence

BAG2
NM_004282.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.523

Publications

4 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:

ZNF451-AS1 (HGNC:53824): (ZNF451 regulatory antisense RNA 1)

ZNF451-AS1 links:

ENSG00000307695 (HGNC:):

ENSG00000307695 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAG2	NM_004282.4	MANE Select	c.113+761A>C		intron	N/A	NP_004273.1	O95816-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAG2	ENST00000370693.5	TSL:1 MANE Select	c.113+761A>C	intron	N/A	ENSP00000359727.4	O95816-1
BAG2	ENST00000965201.1		c.113+761A>C	intron	N/A	ENSP00000635260.1
ZNF451-AS1	ENST00000585414.1	TSL:5	n.501-91T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0891

AC:

13559

AN:

152150

Hom.:

673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.0946

Gnomad SAS

AF:

0.0792

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0823

Gnomad OTH

AF:

0.0793

GnomAD4 exome

AF:

0.0763

AC:

53487

AN:

701104

Hom.:

2119

Cov.:

AF XY:

0.0761

AC XY:

24803

AN XY:

325902

show subpopulations

African (AFR)

AF:

0.0782

AC:

1008

AN:

12882

American (AMR)

AF:

0.0898

AC:

AN:

824

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

157

AN:

4380

East Asian (EAS)

AF:

0.0929

AC:

277

AN:

2982

South Asian (SAS)

AF:

0.0702

AC:

959

AN:

13660

European-Finnish (FIN)

AF:

0.130

AC:

AN:

216

Middle Eastern (MID)

AF:

0.0355

AC:

AN:

1382

European-Non Finnish (NFE)

AF:

0.0768

AC:

49274

AN:

641810

Other (OTH)

AF:

0.0723

AC:

1661

AN:

22968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2275

4550

6826

9101

11376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2462

4924

7386

9848

12310

<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:

0.0892

AC:

13581

AN:

152268

Hom.:

673

Cov.:

AF XY:

0.0912

AC XY:

6790

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0902

AC:

3747

AN:

41536

American (AMR)

AF:

0.0778

AC:

1191

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.0948

AC:

492

AN:

5188

South Asian (SAS)

AF:

0.0793

AC:

383

AN:

4830

European-Finnish (FIN)

AF:

0.172

AC:

1828

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0823

AC:

5600

AN:

68024

Other (OTH)

AF:

0.0799

AC:

169

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

654

1307

1961

2614

3268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0552

Hom.:

Bravo

AF:

0.0821

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.62

PhyloP100

-0.52

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over