rs1113132

Variant names:

• chr11-44231853-G-C
• rs1113132
• NM_207122.2:c.1663-500G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-44231853-G-C
• chr11-44231853-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207122.2(EXT2):​c.1663-500G>C 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 152,052 control chromosomes in the GnomAD database, including 5,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (5567 hom., cov: 32)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507
• Publications: 31 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-44231853-G-C is Benign according to our data. Variant chr11-44231853-G-C is described in ClinVar as Benign. ClinVar VariationId is 263288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 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.1663-500G>C		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.1762-500G>C		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.1693-500G>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.1663-500G>C		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.1693-500G>C		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.1663-500G>C		intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36985 AN: 151934 Hom.: 5550 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.243 AC: 37019 AN: 152052 Hom.: 5567 Cov.: 32 AF XY: 0.251 AC XY: 18644 AN XY: 74314

African (AFR) AF: 0.0924 AC: 3836 AN: 41502

American (AMR) AF: 0.413 AC: 6302 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2107 AN: 5150

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3314 AN: 10558

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18188 AN: 67976

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.247 Hom.: 749

Bravo AF: 0.244

Asia WGS AF: 0.419 AC: 1456 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.41
PhyloP100		-0.51
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: rs1113132; hg19: chr11-44253403;