Variant chr6-26383878-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_006995.5(BTN2A2):c.57G>A(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,780 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 31)

Exomes 𝑓: 0.012 ( 146 hom. )

Consequence

BTN2A2
NM_006995.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.145

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-26383878-G-A is Benign according to our data. Variant chr6-26383878-G-A is described in ClinVar as [Benign]. Clinvar id is 3057121.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.145 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0101 (1531/152120) while in subpopulation AMR AF= 0.0193 (294/15272). AF 95% confidence interval is 0.0174. There are 13 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A2	NM_006995.5 link	c.57G>A	p.Leu19Leu	synonymous_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.57G>A	p.Leu19Leu	synonymous_variant	Exon 2 of 8	1	NM_006995.5	ENSP00000349143.4		Q8WVV5-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1533

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0193

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0114

AC:

2848

AN:

249958

Hom.:

AF XY:

0.0122

AC XY:

1649

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0446

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.00251

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0123

AC:

18026

AN:

1461660

Hom.:

146

Cov.:

AF XY:

0.0126

AC XY:

9177

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0411

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0101

AC:

1531

AN:

152120

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

734

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00239

Gnomad4 AMR

AF:

0.0193

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BTN2A2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

DANN

Benign

0.82

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