19-1987192-G-A

Variant names:

• chr19-1987192-G-A
• NM_017797.4:c.1243C>T

Variant summary

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

The NM_017797.4(BTBD2):​c.1243C>T​(p.Pro415Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTBD2 NM_017797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD2	NM_017797.4	c.1243C>T	p.Pro415Ser	missense_variant	Exon 7 of 9	ENST00000255608.9	NP_060267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD2	ENST00000255608.9	c.1243C>T	p.Pro415Ser	missense_variant	Exon 7 of 9	1	NM_017797.4	ENSP00000255608.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1243C>T (p.P415S) alteration is located in exon 7 (coding exon 7) of the BTBD2 gene. This alteration results from a C to T substitution at nucleotide position 1243, causing the proline (P) at amino acid position 415 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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Uncertain	0.48
Sift	Benign	0.32	T;.
Sift4G	Benign	0.16	T;.
Polyphen		0.99	D;.
Vest4		0.62
MutPred		0.53		Gain of sheet (P = 0.0028);.;
MVP		0.65
MPC		0.72
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.43
gMVP		0.21

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: chr19-1987191;