rs1845618

Variant names:

• chr11-44231787-A-G
• rs1845618
• NM_207122.2:c.1663-566A>G

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.1663-566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,162 control chromosomes in the GnomAD database, including 5,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5637 hom., cov: 32)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897
• Publications: 3 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=-0.88).
• BP6: Variant 11-44231787-A-G is Benign according to our data. Variant chr11-44231787-A-G is described in ClinVar as Benign. ClinVar VariationId is 263289.Status of the report is criteria_provided_single_submitter, 1 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.1663-566A>G		intron	N/A	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.1762-566A>G		intron	N/A	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.1693-566A>G		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.1663-566A>G		intron	N/A	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.1693-566A>G		intron	N/A	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.1663-566A>G		intron	N/A	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37284 AN: 152044 Hom.: 5621 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.245 AC: 37318 AN: 152162 Hom.: 5637 Cov.: 32 AF XY: 0.253 AC XY: 18789 AN XY: 74384

African (AFR) AF: 0.0960 AC: 3989 AN: 41536

American (AMR) AF: 0.414 AC: 6330 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2126 AN: 5170

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3329 AN: 10592

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18239 AN: 67984

Other (OTH) AF: 0.270 AC: 569 AN: 2106

Alfa AF: 0.262 Hom.: 1102

Bravo AF: 0.246

Asia WGS AF: 0.423 AC: 1470 AN: 3478

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	-0.88
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		0.90
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: rs1845618; hg19: chr11-44253337;