rs199672282

Variant names:

• chr1-100874275-G-C
• rs199672282
• NM_001033025.3:c.660C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-100874275-G-C
• chr1-100874275-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033025.3(EXTL2):​c.660C>G​(p.Ser220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXTL2 NM_001033025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

EXTL2 (HGNC:3516): (exostosin like glycosyltransferase 2) Enables alpha-1,4-N-acetylgalactosaminyltransferase activity and glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity. Involved in N-acetylglucosamine metabolic process and UDP-N-acetylgalactosamine metabolic process. Located in cytosol; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17816979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXTL2	NM_001033025.3	c.660C>G	p.Ser220Arg	missense_variant	Exon 5 of 5	ENST00000370114.8	NP_001028197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXTL2	ENST00000370114.8	c.660C>G	p.Ser220Arg	missense_variant	Exon 5 of 5	1	NM_001033025.3	ENSP00000359132.3
EXTL2	ENST00000370113.7	c.660C>G	p.Ser220Arg	missense_variant	Exon 5 of 5	1		ENSP00000359131.3
EXTL2	ENST00000450240.2	c.684C>G	p.Ser228Arg	missense_variant	Exon 6 of 6	4		ENSP00000403363.1
EXTL2	ENST00000535414	c.*145C>G		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000444385.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.45	N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.76	T;T;.
Polyphen		0.032	B;B;.
Vest4		0.14
MutPred		0.62		Gain of methylation at K221 (P = 0.0426);Gain of methylation at K221 (P = 0.0426);.;
MVP		0.74
MPC		0.18
ClinPred		0.36	T
GERP RS		4.0
Varity_R		0.051
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199672282; hg19: chr1-101339831;