6-89932516-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_021813.4(BACH2):c.2418G>C(p.Glu806Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E806Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

BACH2
NM_021813.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.736

Variant links:

Genes affected

BACH2 (HGNC:14078): (BTB domain and CNC homolog 2) Enables sequence-specific double-stranded DNA binding activity. Involved in primary adaptive immune response involving T cells and B cells. Located in cytosol and nucleoplasm. Implicated in immunodeficiency 60. [provided by Alliance of Genome Resources, Apr 2022]

BACH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant where missense usually causes diseases, BACH2

BP4

Computational evidence support a benign effect (MetaRNN=0.0048598647).

BP6

Variant 6-89932516-C-G is Benign according to our data. Variant chr6-89932516-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1662867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACH2	NM_021813.4 linkuse as main transcript	c.2418G>C	p.Glu806Asp	missense_variant	9/9	ENST00000257749.9
BACH2	NM_001170794.2 linkuse as main transcript	c.2418G>C	p.Glu806Asp	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACH2	ENST00000257749.9 linkuse as main transcript	c.2418G>C	p.Glu806Asp	missense_variant	9/9	1	NM_021813.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000235

AC:

AN:

251428

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00323

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00104

AC:

159

AN:

152202

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00359

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000100

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2023

- -

Immunodeficiency 60

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.93

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.066

MutPred

0.11

Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);

MVP

0.49

MPC

0.46

ClinPred

0.011

GERP RS

0.26

Varity_R

0.067

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over