Genetic Variant BTNL2:p.Pro333Thr (chr6-32396120-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001304561.2(BTNL2):c.997C>A(p.Pro333Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.361

Publications

0 publications found

Variant links:

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]

BTNL2 links:

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

TSBP1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027741462).

BP6

Variant 6-32396120-G-T is Benign according to our data. Variant chr6-32396120-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2552449.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.997C>A	p.Pro333Thr	missense	Exon 5 of 8	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-9334G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.997C>A	p.Pro333Thr	missense	Exon 5 of 8	ENSP00000390613.3	Q9UIR0-7
BTNL2	ENST00000465865.6	TSL:1	n.*272C>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000420063.1	F8WDK6
BTNL2	ENST00000544175.3	TSL:1	n.*258C>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000443364.2	Q9UIR0-8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.5

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.010

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.0063

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.54

PhyloP100

-0.36

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.29

REVEL

Benign

0.051

Sift

Benign

0.70

Sift4G

Benign

0.80

Polyphen

0.0010

Vest4

0.023

MutPred

0.42

Gain of phosphorylation at P333 (P = 0.035)

MVP

0.36

MPC

0.41

ClinPred

0.028

GERP RS

-1.4

Varity_R

0.068

gMVP

0.39

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over