6-26385098-G-A

Variant names:

• chr6-26385098-G-A
• rs181037825
• NM_006995.5:c.178G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006995.5(BTN2A2):​c.178G>A​(p.Glu60Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032895327).

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.178G>A	p.Glu60Lys	missense	Exon 3 of 8	NP_008926.2
	BTN2A2	NM_001197237.2		c.178G>A	p.Glu60Lys	missense	Exon 3 of 8	NP_001184166.1	Q8WVV5-1
	BTN2A2	NM_001197238.2		c.178G>A	p.Glu60Lys	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.178G>A	p.Glu60Lys	missense	Exon 3 of 8	ENSP00000349143.4	Q8WVV5-1
	BTN2A2	ENST00000416795.6	TSL:1	c.178G>A	p.Glu60Lys	missense	Exon 3 of 8	ENSP00000399308.2	Q8WVV5-1
	BTN2A2	ENST00000469230.5	TSL:1	c.178G>A	p.Glu60Lys	missense	Exon 3 of 8	ENSP00000417472.1	Q8WVV5-2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251440 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727198

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111940

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74392

African (AFR) AF: 0.000265 AC: 11 AN: 41518

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.094
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N
PhyloP100		1.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.067
Sift	Benign	0.12	T
Sift4G	Benign	0.92	T
Polyphen		0.40	B
Vest4		0.17
MVP		0.17
MPC		0.54
ClinPred		0.093	T
GERP RS		2.7
Varity_R		0.043
gMVP		0.41
Mutation Taster		=95/5	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: rs181037825; hg19: chr6-26385326; COSMIC: COSV107432842;