dbSNP rs11191580: NT5C2:c.102-6975A>G (chr10-103146454-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001351169.2(NT5C2):c.102-6975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 984,390 control chromosomes in the GnomAD database, including 3,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.083 ( 819 hom., cov: 32)

Exomes 𝑓: 0.080 ( 3080 hom. )

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.558

Publications

121 publications found

Variant links:

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

NT5C2 Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 45
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

NT5C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C2	NM_001351169.2	MANE Select	c.102-6975A>G	intron	N/A	NP_001338098.1	P49902-1
NT5C2	NM_001351170.2		c.102-6975A>G	intron	N/A	NP_001338099.1	A0A6Q8PHP0
NT5C2	NM_001351171.2		c.102-6975A>G	intron	N/A	NP_001338100.1	A0A6Q8PHP0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.102-6975A>G	intron	N/A	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.102-6975A>G	intron	N/A	ENSP00000339479.5	P49902-1
NT5C2	ENST00000874311.1		c.102-6975A>G	intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes

AF:

0.0835

AC:

12700

AN:

152156

Hom.:

815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0903

Gnomad OTH

AF:

0.0975

GnomAD4 exome

AF:

0.0797

AC:

66304

AN:

832116

Hom.:

3080

Cov.:

AF XY:

0.0800

AC XY:

30739

AN XY:

384294

show subpopulations

African (AFR)

AF:

0.0107

AC:

169

AN:

15782

American (AMR)

AF:

0.179

AC:

176

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0747

AC:

384

AN:

5138

East Asian (EAS)

AF:

0.275

AC:

997

AN:

3622

South Asian (SAS)

AF:

0.208

AC:

3414

AN:

16396

European-Finnish (FIN)

AF:

0.0833

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0846

AC:

137

AN:

1620

European-Non Finnish (NFE)

AF:

0.0767

AC:

58366

AN:

761052

Other (OTH)

AF:

0.0968

AC:

2638

AN:

27246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

2747

5493

8240

10986

13733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3032

6064

9096

12128

15160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0835

AC:

12709

AN:

152274

Hom.:

819

Cov.:

AF XY:

0.0861

AC XY:

6408

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0212

AC:

883

AN:

41556

American (AMR)

AF:

0.135

AC:

2068

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0720

AC:

250

AN:

3472

East Asian (EAS)

AF:

0.277

AC:

1436

AN:

5184

South Asian (SAS)

AF:

0.184

AC:

886

AN:

4822

European-Finnish (FIN)

AF:

0.0746

AC:

792

AN:

10610

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0904

AC:

6145

AN:

68008

Other (OTH)

AF:

0.100

AC:

212

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

567

1134

1700

2267

2834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0929

Hom.:

2348

Bravo

AF:

0.0855

Asia WGS

AF:

0.193

AC:

670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over