6-26392287-G-C

Variant names:

• chr6-26392287-G-C
• rs2072803
• NM_006995.5:c.980-88G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.078 (585 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10557 hom.)
• Consequence: BTN2A2 NM_006995.5 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.580
• Publications: 25 publications found

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]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3059309.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006995.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN2A2	NM_006995.5	MANE Select	c.980-88G>C		intron	N/A	NP_008926.2
	BTN2A2	NM_001197240.2		c.763G>C	p.Ala255Pro	missense	Exon 7 of 7	NP_001184169.1
	BTN2A2	NM_001197237.2		c.980-88G>C		intron	N/A	NP_001184166.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN2A2	ENST00000356709.9	TSL:1 MANE Select	c.980-88G>C		intron	N/A	ENSP00000349143.4
	BTN2A2	ENST00000416795.6	TSL:1	c.980-88G>C		intron	N/A	ENSP00000399308.2
	BTN2A2	ENST00000469230.5	TSL:1	c.979+1458G>C		intron	N/A	ENSP00000417472.1

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

GnomAD2 exomes AF: 0.0855 AC: 19218 AN: 224716 AF XY: 0.0885

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 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

African (AFR) AF: 0.0352 AC: 1165 AN: 33140

American (AMR) AF: 0.0324 AC: 1373 AN: 42390

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 1154 AN: 25854

East Asian (EAS) AF: 0.132 AC: 5137 AN: 39054

South Asian (SAS) AF: 0.0912 AC: 7716 AN: 84598

European-Finnish (FIN) AF: 0.0834 AC: 4383 AN: 52524

Middle Eastern (MID) AF: 0.0504 AC: 290 AN: 5754

European-Non Finnish (NFE) AF: 0.126 AC: 139797 AN: 1105486

Other (OTH) AF: 0.0994 AC: 5957 AN: 59958

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

African (AFR) AF: 0.0337 AC: 1400 AN: 41552

American (AMR) AF: 0.0391 AC: 599 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3472

East Asian (EAS) AF: 0.102 AC: 526 AN: 5174

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.0782 AC: 830 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7624 AN: 68008

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

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: no assertion criteria provided

Submissions by phenotype

BTN2A2-related disorder Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
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
PhyloP100		0.58
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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