rs11966235

Variant names:

• chr6-169226735-C-T
• rs11966235
• NM_003247.5:c.2420-437G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.2420-437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,056 control chromosomes in the GnomAD database, including 4,574 homozygotes. 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: 𝑓 0.24 (4574 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.2420-437G>A		intron_variant	Intron 15 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.2420-437G>A		intron_variant	Intron 15 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36875 AN: 151938 Hom.: 4558 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36937 AN: 152056 Hom.: 4574 Cov.: 33 AF XY: 0.242 AC XY: 18022 AN XY: 74318

African (AFR) AF: 0.217 AC: 9011 AN: 41478

American (AMR) AF: 0.232 AC: 3549 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5158

South Asian (SAS) AF: 0.335 AC: 1612 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2585 AN: 10552

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17445 AN: 67994

Other (OTH) AF: 0.239 AC: 504 AN: 2106

Alfa AF: 0.253 Hom.: 13019

Bravo AF: 0.240

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.30
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs11966235; hg19: chr6-169626830; COSMIC: COSV64677898; COSMIC: COSV64677898;