6-26385035-C-G

Position:

• chr6-26385035-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006995.5(BTN2A2):​c.115C>G​(p.Pro39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,613,742 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 31)
  • Exomes 𝑓: 0.0068 (59 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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=0.0040212274).
• BP6: Variant 6-26385035-C-G is Benign according to our data. Variant chr6-26385035-C-G is described in ClinVar as [Benign]. Clinvar id is 790030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1782/152162) while in subpopulation AFR AF= 0.0269 (1116/41478). AF 95% confidence interval is 0.0256. There are 30 homozygotes in gnomad4. There are 843 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.115C>G	p.Pro39Ala	missense_variant	3/8	ENST00000356709.9	NP_008926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9	c.115C>G	p.Pro39Ala	missense_variant	3/8	1	NM_006995.5	ENSP00000349143	P1
	ENST00000707189.1	n.1000-168152C>G		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-147670C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1772 AN: 152044 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00668 AC: 1677 AN: 250860 Hom.: 17 AF XY: 0.00606 AC XY: 821 AN XY: 135548

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.00885

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00589

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00680 AC: 9935 AN: 1461580 Hom.: 59 Cov.: 31 AF XY: 0.00647 AC XY: 4705 AN XY: 727090

Gnomad4 AFR exome AF: 0.0288

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.00210

Gnomad4 NFE exome AF: 0.00672

Gnomad4 OTH exome AF: 0.00818

GnomAD4 genome AF: 0.0117 AC: 1782 AN: 152162 Hom.: 30 Cov.: 31 AF XY: 0.0113 AC XY: 843 AN XY: 74380

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00629

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00742 Hom.: 7

Bravo AF: 0.0142

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.00767 AC: 66

ExAC AF: 0.00703 AC: 853

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T;.;.;T;.
Eigen	Benign	0.078
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.91	D;.;D;D;D;D
MetaRNN	Benign	0.0040	T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.3	M;M;.;M;M;.
MutationTaster	Benign	0.56	D;D;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.1	D;D;D;D;D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;D;.
Vest4		0.37
MVP		0.84
MPC		0.63
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.25
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs57038103; hg19: chr6-26385263;