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

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A2	NM_006995.5 link	c.11C>T	p.Ala4Val	missense_variant	Exon 2 of 8	ENST00000356709.9	NP_008926.2	Q8WVV5-1A0A024R038

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9 link	c.11C>T	p.Ala4Val	missense_variant	Exon 2 of 8	1	NM_006995.5	ENSP00000349143.4		Q8WVV5-1

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

GnomAD3 exomes

AF:

0.00669

AC:

1681

AN:

251442

Hom.:

AF XY:

0.00606

AC XY:

824

AN XY:

135900

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 SAS exome

AF:

0.000490

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

Gnomad4 AFR exome

AF:

0.0287

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.00670

Gnomad4 OTH exome

AF:

0.00818

GnomAD4 genome

AF:

0.0117

AC:

1786

AN:

152226

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

845

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.00993

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00760

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 03, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;T;.;.;.;.;.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.83

T;.;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0031

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.63

N;N;N;.;.;N;N;N;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.71

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.13

T;T;D;T;D;D;D;T;T;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D;D;D;D

Polyphen

0.034

B;B;.;.;.;.;.;B;.;.

Vest4

0.17

MVP

0.97

MPC

0.15

ClinPred

0.0044

GERP RS

1.1

Varity_R

0.039

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over