NM_207122.2:c.*101G>C

Variant names:

• chr11-44244388-G-C
• rs117755165
• NM_207122.2:c.*101G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_207122.2(EXT2):​c.*101G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,352,236 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: EXT2 NM_207122.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.627
• Publications: 0 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• seizures-scoliosis-macrocephaly syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.78).
• BP6: Variant 11-44244388-G-C is Benign according to our data. Variant chr11-44244388-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 304597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00332 (505/152314) while in subpopulation NFE AF = 0.00506 (344/68026). AF 95% confidence interval is 0.00462. There are 1 homozygotes in GnomAd4. There are 236 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 24 AD,AR gene

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.*101G>C		3_prime_UTR	Exon 14 of 14	NP_997005.1
	EXT2	NM_000401.3		c.*101G>C		3_prime_UTR	Exon 14 of 14	NP_000392.3
	EXT2	NM_001178083.3		c.*101G>C		3_prime_UTR	Exon 15 of 15	NP_001171554.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT2	ENST00000533608.7	TSL:1 MANE Select	c.*101G>C		3_prime_UTR	Exon 14 of 14	ENSP00000431173.2
	EXT2	ENST00000358681.8	TSL:1	c.*101G>C		3_prime_UTR	Exon 15 of 15	ENSP00000351509.4
	EXT2	ENST00000343631.4	TSL:1	c.*101G>C		3_prime_UTR	Exon 15 of 15	ENSP00000342656.3

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 506 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00458 AC: 5499 AN: 1199922 Hom.: 24 Cov.: 16 AF XY: 0.00449 AC XY: 2726 AN XY: 607476

African (AFR) AF: 0.00138 AC: 39 AN: 28314

American (AMR) AF: 0.00376 AC: 161 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.00481 AC: 117 AN: 24304

East Asian (EAS) AF: 0.00 AC: 0 AN: 38234

South Asian (SAS) AF: 0.000854 AC: 68 AN: 79582

European-Finnish (FIN) AF: 0.000795 AC: 40 AN: 50302

Middle Eastern (MID) AF: 0.00859 AC: 39 AN: 4540

European-Non Finnish (NFE) AF: 0.00546 AC: 4809 AN: 880054

Other (OTH) AF: 0.00437 AC: 226 AN: 51768

GnomAD4 genome AF: 0.00332 AC: 505 AN: 152314 Hom.: 1 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74494

African (AFR) AF: 0.00111 AC: 46 AN: 41566

American (AMR) AF: 0.00477 AC: 73 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00506 AC: 344 AN: 68026

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00318 Hom.: 0

Bravo AF: 0.00345

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Exostoses, multiple, type 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.80
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs117755165; hg19: chr11-44265938;