rs147352494

Variant names:

• chr19-1986919-C-A
• rs147352494
• NM_017797.4:c.1327G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-1986919-C-A
• chr19-1986919-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017797.4(BTBD2):​c.1327G>T​(p.Asp443Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,994 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D443N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTBD2 NM_017797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07
• Publications: 0 publications found

Genes affected

BTBD2 (HGNC:15504): (BTB domain containing 2) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.991

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017797.4. 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
	BTBD2	NM_017797.4	MANE Select	c.1327G>T	p.Asp443Tyr	missense	Exon 8 of 9	NP_060267.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD2	ENST00000255608.9	TSL:1 MANE Select	c.1327G>T	p.Asp443Tyr	missense	Exon 8 of 9	ENSP00000255608.3	Q9BX70-1
	BTBD2	ENST00000589685.2	TSL:1	n.1121G>T		non_coding_transcript_exon	Exon 5 of 6
	BTBD2	ENST00000936983.1		c.1207G>T	p.Asp403Tyr	missense	Exon 7 of 8	ENSP00000607042.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460994 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726794

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-8.5	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.94		Loss of disorder (P = 0.0158)
MVP		0.96
MPC		1.6
ClinPred		1.0	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.95
gMVP		0.63
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs147352494; hg19: chr19-1986918;