chr6-26459733-T-A

Variant names:

• chr6-26459733-T-A
• NM_007049.5:c.335T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007049.5(BTN2A1):​c.335T>A​(p.Ile112Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55

Genes affected

BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ENSG00000291336 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5	c.335T>A	p.Ile112Lys	missense_variant	Exon 3 of 8	ENST00000312541.10	NP_008980.1
BTN2A1	NM_001197233.3	c.152T>A	p.Ile51Lys	missense_variant	Exon 2 of 7		NP_001184162.1
BTN2A1	NM_078476.4	c.335T>A	p.Ile112Lys	missense_variant	Exon 3 of 8		NP_510961.1
BTN2A1	NM_001197234.3	c.335T>A	p.Ile112Lys	missense_variant	Exon 3 of 8		NP_001184163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10	c.335T>A	p.Ile112Lys	missense_variant	Exon 3 of 8	1	NM_007049.5	ENSP00000312158.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.26	.;T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	.;H;.;H;H
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.2	D;D;D;D;D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.87
MutPred		0.84		.;Gain of MoRF binding (P = 0.0211);.;Gain of MoRF binding (P = 0.0211);Gain of MoRF binding (P = 0.0211);
MVP		0.48
MPC		0.52
ClinPred		1.0	D
GERP RS		1.8
Varity_R		0.96
gMVP		0.77

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: chr6-26459961;