6-26385105-A-G

Variant names:

• chr6-26385105-A-G
• NM_006995.5:c.185A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006995.5(BTN2A2):​c.185A>G​(p.Asn62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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]

ENSG00000291336 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026715457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.185A>G	p.Asn62Ser	missense_variant	Exon 3 of 8	ENST00000356709.9	NP_008926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9	c.185A>G	p.Asn62Ser	missense_variant	Exon 3 of 8	1	NM_006995.5	ENSP00000349143.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727210

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.7
DANN	Benign	0.30
DEOGEN2	Benign	0.015	.;T;.;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.85	D;.;D;T;D;D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.027	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.050	N;N;.;N;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.77	N;N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.98	T;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.086	B;B;.;.;B;.
Vest4		0.097
MutPred		0.29		Gain of phosphorylation at N62 (P = 0.0582);Gain of phosphorylation at N62 (P = 0.0582);Gain of phosphorylation at N62 (P = 0.0582);Gain of phosphorylation at N62 (P = 0.0582);Gain of phosphorylation at N62 (P = 0.0582);Gain of phosphorylation at N62 (P = 0.0582);
MVP		0.28
MPC		0.13
ClinPred		0.051	T
GERP RS		-4.3
Varity_R		0.018
gMVP		0.24

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: chr6-26385333;