6-26385035-C-A

Position:

• chr6-26385035-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006995.5(BTN2A2):​c.115C>A​(p.Pro39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.115C>A	p.Pro39Thr	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>A	p.Pro39Thr	missense_variant	3/8	1	NM_006995.5	ENSP00000349143	P1
	ENST00000707189.1	n.1000-168152C>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-147670C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461592 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.115C>A (p.P39T) alteration is located in exon 3 (coding exon 2) of the BTN2A2 gene. This alteration results from a C to A substitution at nucleotide position 115, causing the proline (P) at amino acid position 39 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	0.0050	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.;.;T;.
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.36	N
LIST_S2	Pathogenic	0.97	D;.;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.0	M;M;.;M;M;.
MutationTaster	Benign	0.56	D;D;N;N;N;N
PrimateAI	Benign	0.44	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	0.0060	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;D;.
Vest4		0.46
MutPred		0.67		Gain of glycosylation at P39 (P = 0.0349);Gain of glycosylation at P39 (P = 0.0349);Gain of glycosylation at P39 (P = 0.0349);Gain of glycosylation at P39 (P = 0.0349);Gain of glycosylation at P39 (P = 0.0349);Gain of glycosylation at P39 (P = 0.0349);
MVP		0.79
MPC		0.68
ClinPred		0.97	D
GERP RS		2.7
Varity_R		0.53
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-26385263;