chr6-89932516-C-G

Variant names:

• chr6-89932516-C-G
• rs141976854
• NM_021813.4:c.2418G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 14/22 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. E806G) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.736
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 60

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• 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 VariationId is 1662867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 159 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021813.4. 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
	BACH2	NM_021813.4	MANE Select	c.2418G>C	p.Glu806Asp	missense	Exon 9 of 9	NP_068585.1	Q9BYV9
	BACH2	NM_001170794.2		c.2418G>C	p.Glu806Asp	missense	Exon 7 of 7	NP_001164265.1	Q9BYV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	ENST00000257749.9	TSL:1 MANE Select	c.2418G>C	p.Glu806Asp	missense	Exon 9 of 9	ENSP00000257749.4	Q9BYV9
	BACH2	ENST00000343122.7	TSL:5	c.2418G>C	p.Glu806Asp	missense	Exon 7 of 7	ENSP00000345642.3	Q9BYV9
	BACH2	ENST00000406998.7	TSL:2	c.2418G>C	p.Glu806Asp	missense	Exon 7 of 7	ENSP00000384145.3	Q9BYV9

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152084 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000235 AC: 59 AN: 251428 AF XY: 0.000177

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 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.: 0 Cov.: 30 AF XY: 0.0000921 AC XY: 67 AN XY: 727246

African (AFR) AF: 0.00323 AC: 108 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112012

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152202 Hom.: 0 Cov.: 31 AF XY: 0.000994 AC XY: 74 AN XY: 74412

African (AFR) AF: 0.00359 AC: 149 AN: 41532

American (AMR) AF: 0.000393 AC: 6 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.00106

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000321 AC: 39

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Immunodeficiency 60 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.74
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.091
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.066
MutPred		0.11		Loss of loop (P = 0.0203)
MVP		0.49
MPC		0.46
ClinPred		0.011	T
GERP RS		0.26
Varity_R		0.067
gMVP		0.21
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs141976854; hg19: chr6-90642235;