chr6-26385317-G-A

Variant names:

• chr6-26385317-G-A
• NM_006995.5:c.397G>A

Variant summary

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

The NM_006995.5(BTN2A2):​c.397G>A​(p.Glu133Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0210
• Publications: 0 publications found

Genes affected

BTN2A2 (HGNC:1137): (butyrophilin subfamily 2 member A2) Butyrophilin is the major protein associated with fat droplets in the milk. This gene is a member of the BTN2 subfamily of genes, which encode proteins belonging to the butyrophilin protein family. The gene is located in a cluster on chromosome 6, consisting of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The encoded protein is a type I receptor glycoprotein involved in lipid, fatty-acid and sterol metabolism. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ENSG00000291336 (HGNC:):

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=0.1078442).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006995.5. 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
	BTN2A2	NM_006995.5	MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	NP_008926.2
	BTN2A2	NM_001197237.2		c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	NP_001184166.1	Q8WVV5-1
	BTN2A2	NM_001197238.2		c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	NP_001184167.1	Q8WVV5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN2A2	ENST00000356709.9	TSL:1 MANE Select	c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	ENSP00000349143.4	Q8WVV5-1
	BTN2A2	ENST00000416795.6	TSL:1	c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	ENSP00000399308.2	Q8WVV5-1
	BTN2A2	ENST00000469230.5	TSL:1	c.397G>A	p.Glu133Lys	missense	Exon 3 of 8	ENSP00000417472.1	Q8WVV5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.021
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.076
Sift	Benign	0.30	T
Sift4G	Benign	0.25	T
Polyphen		0.97	D
Vest4		0.27
MutPred		0.59		Gain of ubiquitination at E133 (P = 0.0258)
MVP		0.14
MPC		0.62
ClinPred		0.57	D
GERP RS		2.9
Varity_R		0.094
gMVP		0.34
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

hg19: chr6-26385545;