dbSNP rs73736234: BTN2A2:p.Ala4Val (chr6-26383832-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006995.5(BTN2A2):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,614,050 control chromosomes in the GnomAD database, including 90 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 60 hom. )

Consequence

BTN2A2
NM_006995.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.566

Publications

8 publications found

Variant links:

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]

BTN2A2 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003088057).

BP6

Variant 6-26383832-C-T is Benign according to our data. Variant chr6-26383832-C-T is described in ClinVar as Benign. ClinVar VariationId is 790029.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1786/152226) while in subpopulation AFR AF = 0.027 (1119/41516). AF 95% confidence interval is 0.0256. There are 30 homozygotes in GnomAd4. There are 845 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTN2A2	NM_006995.5	MANE Select	c.11C>T	p.Ala4Val	missense	Exon 2 of 8	NP_008926.2
BTN2A2	NM_001197237.2		c.11C>T	p.Ala4Val	missense	Exon 2 of 8	NP_001184166.1	Q8WVV5-1
BTN2A2	NM_181531.3		c.11C>T	p.Ala4Val	missense	Exon 2 of 7	NP_853509.1	Q8WVV5-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTN2A2	ENST00000356709.9	TSL:1 MANE Select	c.11C>T	p.Ala4Val	missense	Exon 2 of 8	ENSP00000349143.4	Q8WVV5-1
BTN2A2	ENST00000416795.6	TSL:1	c.11C>T	p.Ala4Val	missense	Exon 2 of 8	ENSP00000399308.2	Q8WVV5-1
BTN2A2	ENST00000469230.5	TSL:1	c.11C>T	p.Ala4Val	missense	Exon 2 of 8	ENSP00000417472.1	Q8WVV5-2

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1776

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.00669

AC:

1681

AN:

251442

AF XY:

0.00606

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00589

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00678

AC:

9913

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

4700

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0287

AC:

962

AN:

33470

American (AMR)

AF:

0.0101

AC:

450

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

347

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000556

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00210

AC:

112

AN:

53418

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00670

AC:

7451

AN:

1111956

Other (OTH)

AF:

0.00818

AC:

494

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

543

1086

1630

2173

2716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0117

AC:

1786

AN:

152226

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

845

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0270

AC:

1119

AN:

41516

American (AMR)

AF:

0.00993

AC:

152

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00629

AC:

428

AN:

68008

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

162

243

324

405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00875

Hom.:

Bravo

AF:

0.0141

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.0250

AC:

110

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00702

AC:

852

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.63

PhyloP100

0.57

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.71

REVEL

Benign

0.052

Sift

Benign

0.13

Sift4G

Uncertain

0.012

Polyphen

0.034

Vest4

0.17

MVP

0.97

MPC

0.15

ClinPred

0.0044

GERP RS

1.1

PromoterAI

0.023

Neutral

(source)

Varity_R

0.039

gMVP

0.51

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over