6-89932526-G-C

Variant names:

• chr6-89932526-G-C
• rs769816700
• NM_021813.4:c.2408C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021813.4(BACH2):​c.2408C>G​(p.Thr803Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T803I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BACH2 NM_021813.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06869072).

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.2408C>G	p.Thr803Ser	missense	Exon 9 of 9	NP_068585.1	Q9BYV9
	BACH2	NM_001170794.2		c.2408C>G	p.Thr803Ser	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.2408C>G	p.Thr803Ser	missense	Exon 9 of 9	ENSP00000257749.4	Q9BYV9
	BACH2	ENST00000343122.7	TSL:5	c.2408C>G	p.Thr803Ser	missense	Exon 7 of 7	ENSP00000345642.3	Q9BYV9
	BACH2	ENST00000406998.7	TSL:2	c.2408C>G	p.Thr803Ser	missense	Exon 7 of 7	ENSP00000384145.3	Q9BYV9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.9
DANN	Benign	0.89
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.40	T
Polyphen		0.010	B
Vest4		0.057
MutPred		0.088		Gain of helix (P = 0.0093)
MVP		0.45
MPC		0.46
ClinPred		0.096	T
GERP RS		1.5
Varity_R		0.031
gMVP		0.13
Mutation Taster		=99/1	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: rs769816700; hg19: chr6-90642245;