6-32407084-C-A

Variant summary

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

The NM_001304561.2(BTNL2):c.40G>T(p.Ala14Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTNL2 NM_001304561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

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=0.2254276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.40G>T	p.Ala14Ser	missense_variant	1/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.1374C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.40G>T	p.Ala14Ser	missense_variant	1/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.1823C>A		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 16, 2022

The c.40G>T (p.A14S) alteration is located in exon 1 (coding exon 1) of the BTNL2 gene. This alteration results from a G to T substitution at nucleotide position 40, causing the alanine (A) at amino acid position 14 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N;N;N
Sift	Uncertain	0.024	D;T;T
Sift4G	Uncertain	0.039	D;T;.
Polyphen		1.0	.;D;.
Vest4		0.42
MutPred		0.43		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.23
MPC		0.56
ClinPred		0.33	T
GERP RS		2.5
Varity_R		0.024
gMVP		0.23

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: chr6-32374861;