Variant 6-26385302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006995.5(BTN2A2):c.382C>T(p.Arg128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

BTN2A2
NM_006995.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.693

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032101244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN2A2	NM_006995.5 linkuse as main transcript	c.382C>T	p.Arg128Cys	missense_variant	3/8	ENST00000356709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN2A2	ENST00000356709.9 linkuse as main transcript	c.382C>T	p.Arg128Cys	missense_variant	3/8	1	NM_006995.5	P1	Q8WVV5-1
	ENST00000707189.1 linkuse as main transcript	n.1000-167885C>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-147403C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251288

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.382C>T (p.R128C) alteration is located in exon 3 (coding exon 2) of the BTN2A2 gene. This alteration results from a C to T substitution at nucleotide position 382, causing the arginine (R) at amino acid position 128 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.18

T;.;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.032

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.98

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.035

B;B;.;.;B

Vest4

0.10

MutPred

0.52

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.37

MPC

0.21

ClinPred

0.023

GERP RS

0.90

Varity_R

0.049

gMVP

0.23

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

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