dbSNP rs709160: TSEN2:c.-18+23G>C (chr3-12484903-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025265.4(TSEN2):c.-18+23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,124 control chromosomes in the GnomAD database, including 24,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24461 hom., cov: 32)

Exomes 𝑓: 0.37 ( 3 hom. )

Consequence

TSEN2
NM_025265.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.11

Publications

8 publications found

Variant links:

Genes affected

TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

TSEN2 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 2B
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-12484903-G-C is Benign according to our data. Variant chr3-12484903-G-C is described in ClinVar as Benign. ClinVar VariationId is 1273097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4 link	c.-18+23G>C		intron_variant	Intron 1 of 11	ENST00000284995.11	NP_079541.1	Q8NCE0-1A0A024R2G3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11 link	c.-18+23G>C		intron_variant	Intron 1 of 11	1	NM_025265.4	ENSP00000284995.6		Q8NCE0-1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82938

AN:

151968

Hom.:

24432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.368

AC:

AN:

Hom.:

Cov.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.643

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.546

AC:

83009

AN:

152086

Hom.:

24461

Cov.:

AF XY:

0.538

AC XY:

40016

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.762

AC:

31615

AN:

41494

American (AMR)

AF:

0.453

AC:

6925

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1823

AN:

3470

East Asian (EAS)

AF:

0.130

AC:

673

AN:

5166

South Asian (SAS)

AF:

0.258

AC:

1245

AN:

4818

European-Finnish (FIN)

AF:

0.495

AC:

5232

AN:

10564

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33764

AN:

67980

Other (OTH)

AF:

0.537

AC:

1133

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1784

3568

5353

7137

8921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.515

Hom.:

2508

Bravo

AF:

0.552

Asia WGS

AF:

0.321

AC:

1117

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 28, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.66

(source)

DANN

Benign

0.51

PhyloP100

-2.1

PromoterAI

-0.037

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over