6-26383900-T-C

Position:

• chr6-26383900-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006995.5(BTN2A2):​c.79T>C​(p.Cys27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.870

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23252887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.79T>C	p.Cys27Arg	missense_variant	2/8	ENST00000356709.9	NP_008926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9	c.79T>C	p.Cys27Arg	missense_variant	2/8	1	NM_006995.5	ENSP00000349143.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 30, 2024

The c.79T>C (p.C27R) alteration is located in exon 2 (coding exon 1) of the BTN2A2 gene. This alteration results from a T to C substitution at nucleotide position 79, causing the cysteine (C) at amino acid position 27 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	1.5
DANN	Benign	0.79
DEOGEN2	Benign	0.032	.;T;.;.;.;.;.;T;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.14	T;.;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.34	N;N;N;.;.;N;N;N;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D;N;N;D;N;N;D;N;D;N
REVEL	Benign	0.16
Sift	Benign	0.34	T;T;T;T;T;T;D;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T;D;T;D;T
Polyphen		0.57	P;B;.;.;.;.;.;B;.;.
Vest4		0.13
MutPred		0.70		Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);Gain of methylation at C27 (P = 0.0206);
MVP		0.72
MPC		0.26
ClinPred		0.069	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.088
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-26384128;