rs77554103

Variant names:

• chr11-44244343-G-A
• rs77554103
• NM_207122.2:c.*56G>A

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.*56G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,592,502 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0055 (251 hom.)
• Consequence: EXT2 NM_207122.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.385
• Publications: 4 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=-0.79).
• BP6: Variant 11-44244343-G-A is Benign according to our data. Variant chr11-44244343-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 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.*56G>A		3_prime_UTR	Exon 14 of 14	NP_997005.1	Q93063-1
	EXT2	NM_000401.3		c.*56G>A		3_prime_UTR	Exon 14 of 14	NP_000392.3	Q93063-3
	EXT2	NM_001178083.3		c.*56G>A		3_prime_UTR	Exon 15 of 15	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.*56G>A		3_prime_UTR	Exon 14 of 14	ENSP00000431173.2	Q93063-1
	EXT2	ENST00000358681.8	TSL:1	c.*56G>A		3_prime_UTR	Exon 15 of 15	ENSP00000351509.4	Q93063-2
	EXT2	ENST00000343631.4	TSL:1	c.*56G>A		3_prime_UTR	Exon 15 of 15	ENSP00000342656.3	Q93063-1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152190 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00550 AC: 7928 AN: 1440194 Hom.: 251 Cov.: 26 AF XY: 0.00552 AC XY: 3958 AN XY: 717634

African (AFR) AF: 0.000575 AC: 19 AN: 33044

American (AMR) AF: 0.0407 AC: 1819 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00135 AC: 35 AN: 25986

East Asian (EAS) AF: 0.0797 AC: 3154 AN: 39574

South Asian (SAS) AF: 0.0114 AC: 973 AN: 85716

European-Finnish (FIN) AF: 0.00160 AC: 85 AN: 53252

Middle Eastern (MID) AF: 0.0104 AC: 59 AN: 5680

European-Non Finnish (NFE) AF: 0.00134 AC: 1465 AN: 1092652

Other (OTH) AF: 0.00535 AC: 319 AN: 59604

GnomAD4 genome AF: 0.00494 AC: 753 AN: 152308 Hom.: 7 Cov.: 31 AF XY: 0.00528 AC XY: 393 AN XY: 74466

African (AFR) AF: 0.00118 AC: 49 AN: 41574

American (AMR) AF: 0.0168 AC: 257 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.0431 AC: 223 AN: 5174

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4824

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 68024

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00378 Hom.: 2

Bravo AF: 0.00650

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.48
PhyloP100		0.39
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: rs77554103; hg19: chr11-44265893; COSMIC: COSV59151511; COSMIC: COSV59151511;