Variant 6-26388144-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006995.5(BTN2A2):c.574G>T(p.Ala192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,614,184 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 3 hom. )

Consequence

BTN2A2
NM_006995.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.863

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056805015).

BP6

Variant 6-26388144-G-T is Benign according to our data. Variant chr6-26388144-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051820.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN2A2	NM_006995.5 linkuse as main transcript	c.574G>T	p.Ala192Ser	missense_variant	4/8	ENST00000356709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN2A2	ENST00000356709.9 linkuse as main transcript	c.574G>T	p.Ala192Ser	missense_variant	4/8	1	NM_006995.5	P1	Q8WVV5-1
	ENST00000707189.1 linkuse as main transcript	n.1000-165043G>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-144561G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000861

AC:

131

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00121

AC:

305

AN:

251470

Hom.:

AF XY:

0.00132

AC XY:

180

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000972

AC:

1421

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

756

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000870

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000860

AC:

131

AN:

152292

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BTN2A2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.031

DANN

Benign

0.64

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.49

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

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0057

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

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

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.22

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

REVEL

Benign

0.085

Sift

Benign

1.0

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

Sift4G

Benign

0.79

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

Polyphen

0.13

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

Vest4

0.083

MVP

0.49

MPC

0.24

ClinPred

0.0094

GERP RS

-7.0

Varity_R

0.11

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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