Genetic Variant BTN2A1:p.Gly199Ser (chr6-26463408-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007049.5(BTN2A1):c.595G>A(p.Gly199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

BTN2A1
NM_007049.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

BTN2A1 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12674662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5 link	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 8	ENST00000312541.10	NP_008980.1	Q7KYR7-2
BTN2A1	NM_001197233.3 link	c.412G>A	p.Gly138Ser	missense_variant	Exon 3 of 7		NP_001184162.1	Q7KYR7-5
BTN2A1	NM_078476.4 link	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 8		NP_510961.1	Q7KYR7-4
BTN2A1	NM_001197234.3 link	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 8		NP_001184163.1	Q7KYR7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10 link	c.595G>A	p.Gly199Ser	missense_variant	Exon 4 of 8	1	NM_007049.5	ENSP00000312158.5		Q7KYR7-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251480

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.595G>A (p.G199S) alteration is located in exon 4 (coding exon 3) of the BTN2A1 gene. This alteration results from a G to A substitution at nucleotide position 595, causing the glycine (G) at amino acid position 199 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

.;T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;M;M;M

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.0

D;D;D;D

REVEL

Benign

0.095

Sift

Benign

0.041

D;D;D;D

Sift4G

Uncertain

0.036

D;D;T;T

Polyphen

0.98

.;D;.;.

Vest4

0.23

MVP

0.26

MPC

0.34

ClinPred

0.77

GERP RS

1.1

Varity_R

0.23

gMVP

0.46

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