rs3740878

Variant names:

• chr11-44236252-T-C
• rs3740878
• NM_207122.2:c.1936-41T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-44236252-T-C
• chr11-44236252-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.1936-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,580,138 control chromosomes in the GnomAD database, including 70,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5665 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64842 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.481
• Publications: 41 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=-0.87).
• BP6: Variant 11-44236252-T-C is Benign according to our data. Variant chr11-44236252-T-C is described in ClinVar as Benign. ClinVar VariationId is 263290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 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.1936-41T>C		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.2035-41T>C		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.1966-41T>C		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.1936-41T>C		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.1966-41T>C		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.1936-41T>C		intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37388 AN: 151972 Hom.: 5648 Cov.: 32

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.318 AC: 79304 AN: 249662 AF XY: 0.315

Gnomad AFR exome AF: 0.0891

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.292 AC: 417325 AN: 1428046 Hom.: 64842 Cov.: 24 AF XY: 0.293 AC XY: 208986 AN XY: 712592

African (AFR) AF: 0.0822 AC: 2691 AN: 32742

American (AMR) AF: 0.520 AC: 23201 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4960 AN: 25918

East Asian (EAS) AF: 0.398 AC: 15737 AN: 39524

South Asian (SAS) AF: 0.369 AC: 31579 AN: 85624

European-Finnish (FIN) AF: 0.307 AC: 16179 AN: 52734

Middle Eastern (MID) AF: 0.181 AC: 1030 AN: 5702

European-Non Finnish (NFE) AF: 0.282 AC: 305246 AN: 1081846

Other (OTH) AF: 0.282 AC: 16702 AN: 59300

GnomAD4 genome AF: 0.246 AC: 37424 AN: 152092 Hom.: 5665 Cov.: 32 AF XY: 0.253 AC XY: 18838 AN XY: 74338

African (AFR) AF: 0.0963 AC: 3998 AN: 41506

American (AMR) AF: 0.415 AC: 6341 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3462

East Asian (EAS) AF: 0.414 AC: 2133 AN: 5152

South Asian (SAS) AF: 0.359 AC: 1733 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3327 AN: 10564

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18310 AN: 67986

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.254 Hom.: 2921

Bravo AF: 0.246

Asia WGS AF: 0.425 AC: 1476 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)
-	-	1	Exostoses, multiple, type 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		-0.48
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: rs3740878; hg19: chr11-44257802; COSMIC: COSV59147143; COSMIC: COSV59147143;