rs11037882

Variant names:

• chr11-44130027-T-A
• rs11037882
• NM_207122.2:c.1080-18T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-44130027-T-A
• chr11-44130027-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207122.2(EXT2):​c.1080-18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,601,054 control chromosomes in the GnomAD database, including 82,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6498 hom., cov: 32)
  • Exomes 𝑓: 0.31 (75688 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.363
• Publications: 12 publications found

Genes affected

EXT2 (HGNC:3513): (exostosin glycosyltransferase 2) This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

EXT2 Gene-Disease associations (from GenCC):

• exostoses, multiple, type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, Ambry Genetics
• seizures-scoliosis-macrocephaly syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary multiple osteochondromas

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-44130027-T-A is Benign according to our data. Variant chr11-44130027-T-A is described in ClinVar as Benign. ClinVar VariationId is 198636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207122.2. 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
	EXT2	NM_207122.2	MANE Select	c.1080-18T>A		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.1179-18T>A		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.1080-18T>A		intron	N/A	NP_001171554.1	Q93063-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT2	ENST00000533608.7	TSL:1 MANE Select	c.1080-18T>A		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.1080-18T>A		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.1080-18T>A		intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40838 AN: 151934 Hom.: 6478 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.343 AC: 86193 AN: 251202 AF XY: 0.338

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.458

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.314 AC: 454857 AN: 1449002 Hom.: 75688 Cov.: 29 AF XY: 0.315 AC XY: 227214 AN XY: 721714

African (AFR) AF: 0.108 AC: 3582 AN: 33228

American (AMR) AF: 0.572 AC: 25575 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5618 AN: 26064

East Asian (EAS) AF: 0.434 AC: 17204 AN: 39622

South Asian (SAS) AF: 0.387 AC: 33262 AN: 85984

European-Finnish (FIN) AF: 0.313 AC: 16698 AN: 53402

Middle Eastern (MID) AF: 0.227 AC: 1306 AN: 5754

European-Non Finnish (NFE) AF: 0.303 AC: 333449 AN: 1100282

Other (OTH) AF: 0.303 AC: 18163 AN: 59974

GnomAD4 genome AF: 0.269 AC: 40873 AN: 152052 Hom.: 6498 Cov.: 32 AF XY: 0.276 AC XY: 20487 AN XY: 74308

African (AFR) AF: 0.122 AC: 5048 AN: 41494

American (AMR) AF: 0.448 AC: 6844 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5158

South Asian (SAS) AF: 0.378 AC: 1819 AN: 4814

European-Finnish (FIN) AF: 0.317 AC: 3349 AN: 10562

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19768 AN: 67964

Other (OTH) AF: 0.295 AC: 622 AN: 2112

Alfa AF: 0.265 Hom.: 1092

Bravo AF: 0.273

Asia WGS AF: 0.448 AC: 1555 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Exostoses, multiple, type 2 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Exostoses, multiple, type 1 (1)
-	-	1	Seizures-scoliosis-macrocephaly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11037882; hg19: chr11-44151577; COSMIC: COSV59147132; COSMIC: COSV59147132;