Variant 17-61874956-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001351695.2(INTS2):c.2539A>T(p.Ile847Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00107 in 1,598,324 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 9 hom. )

Consequence

INTS2
NM_001351695.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.44

Variant links:

Genes affected

INTS2 (HGNC:29241): (integrator complex subunit 2) INTS2 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS2 links:

INTS2 (HGNC:):

INTS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054608583).

BP6

Variant 17-61874956-T-A is Benign according to our data. Variant chr17-61874956-T-A is described in ClinVar as [Benign]. Clinvar id is 726342.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00584 (889/152322) while in subpopulation AFR AF= 0.02 (831/41572). AF 95% confidence interval is 0.0189. There are 5 homozygotes in gnomad4. There are 397 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS2	NM_001351695.2 linkuse as main transcript	c.2539A>T	p.Ile847Leu	missense_variant	19/25	ENST00000251334.7	NP_001338624.2
INTS2	NM_020748.4 linkuse as main transcript	c.2563A>T	p.Ile855Leu	missense_variant	19/25		NP_065799.2	Q9H0H0
INTS2	NM_001330417.2 linkuse as main transcript	c.2539A>T	p.Ile847Leu	missense_variant	19/25		NP_001317346.2	Q9H0H0A0A024QZ48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS2	ENST00000251334.7 linkuse as main transcript	c.2539A>T	p.Ile847Leu	missense_variant	19/25	2	NM_001351695.2	ENSP00000251334.6		J3KMZ7

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

886

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00145

AC:

328

AN:

226120

Hom.:

AF XY:

0.00114

AC XY:

139

AN XY:

121890

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.000937

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000298

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000571

AC:

825

AN:

1446002

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

323

AN XY:

717814

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000839

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00584

AC:

889

AN:

152322

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

397

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.00710

ESP6500AA

AF:

0.0183

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.00157

AC:

190

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.024

T;T;T;T

Eigen

Benign

-0.093

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;.;.;D

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.32

.;N;.;.

REVEL

Benign

0.038

Sift

Benign

1.0

.;T;.;.

Sift4G

Benign

0.95

T;T;.;T

Polyphen

0.047

B;B;.;.

Vest4

0.39

MutPred

0.28

Gain of catalytic residue at I855 (P = 0.0179);Gain of catalytic residue at I855 (P = 0.0179);.;.;

MVP

0.20

MPC

0.26

ClinPred

0.020

GERP RS

5.1

Varity_R

0.47

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over