6-169217631-A-T

Variant names:

• chr6-169217631-A-T
• rs8089
• NM_003247.5:c.*191T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003247.5(THBS2):​c.*191T>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THBS2 NM_003247.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 0 publications found

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.*191T>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.*191T>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 393636 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 204572

African (AFR) AF: 0.00 AC: 0 AN: 10458

American (AMR) AF: 0.00 AC: 0 AN: 11694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11966

East Asian (EAS) AF: 0.00 AC: 0 AN: 27198

South Asian (SAS) AF: 0.00 AC: 0 AN: 25724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1778

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 241942

Other (OTH) AF: 0.00 AC: 0 AN: 22684

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		0.40

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

Other links and lift over

dbSNP: rs8089; hg19: chr6-169617726;