rs2072803

chr6-26392287-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006995.5(BTN2A2):c.980-88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,601,016 control chromosomes in the GnomAD database, including 11,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (585 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10557 hom.)
• Consequence: BTN2A2 NM_006995.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.580

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015104413).
• BP6: Variant 6-26392287-G-C is Benign according to our data. Variant chr6-26392287-G-C is described in ClinVar as [Benign]. Clinvar id is 3059309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN2A2	NM_006995.5	c.980-88G>C		intron_variant		ENST00000356709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN2A2	ENST00000356709.9	c.980-88G>C		intron_variant		1	NM_006995.5	P1
	ENST00000707189.1	n.1000-160900G>C		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-140418G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11948 AN: 152140 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0651

GnomAD3 exomes AF: 0.0855 AC: 19218 AN: 224716 Hom.: 963 AF XY: 0.0885 AC XY: 10788 AN XY: 121840

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.0326

Gnomad ASJ exome AF: 0.0419

Gnomad EAS exome AF: 0.0955

Gnomad SAS exome AF: 0.0925

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.0759

GnomAD4 exome AF: 0.115 AC: 166972 AN: 1448758 Hom.: 10557 Cov.: 30 AF XY: 0.114 AC XY: 82158 AN XY: 719436

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0446

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0834

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.0994

GnomAD4 genome AF: 0.0784 AC: 11939 AN: 152258 Hom.: 585 Cov.: 32 AF XY: 0.0757 AC XY: 5632 AN XY: 74442

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.0391

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0782

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.106 Hom.: 553

Bravo AF: 0.0731

TwinsUK AF: 0.149 AC: 552

ALSPAC AF: 0.138 AC: 531

ExAC AF: 0.0825 AC: 9981

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BTN2A2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 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_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	3.9
Dann	Benign	0.46
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Vest4		0.061
ClinPred		0.010	T
GERP RS		-2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2072803; hg19: chr6-26392515; COSMIC: COSV61856661; COSMIC: COSV61856661;