dbSNP rs753765: INTS2:p.Gln583Gln (chr17-61891639-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001351695.2(INTS2):c.1749A>G(p.Gln583Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 1,612,594 control chromosomes in the GnomAD database, including 8,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.066 ( 587 hom., cov: 31)

Exomes 𝑓: 0.079 ( 7504 hom. )

Consequence

INTS2
NM_001351695.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.314

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:

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 (BayesDel_noAF=-0.56).

BP6

Variant 17-61891639-T-C is Benign according to our data. Variant chr17-61891639-T-C is described in ClinVar as [Benign]. Clinvar id is 3059600.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.314 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS2	NM_001351695.2 link	c.1749A>G	p.Gln583Gln	synonymous_variant	Exon 14 of 25	ENST00000251334.7	NP_001338624.2
INTS2	NM_020748.4 link	c.1773A>G	p.Gln591Gln	synonymous_variant	Exon 14 of 25		NP_065799.2	Q9H0H0
INTS2	NM_001330417.2 link	c.1749A>G	p.Gln583Gln	synonymous_variant	Exon 14 of 25		NP_001317346.2	Q9H0H0A0A024QZ48
INTS2	XR_934509.3 link	n.1815A>G		non_coding_transcript_exon_variant	Exon 14 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS2	ENST00000251334.7 link	c.1749A>G	p.Gln583Gln	synonymous_variant	Exon 14 of 25	2	NM_001351695.2	ENSP00000251334.6		J3KMZ7

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10065

AN:

152026

Hom.:

587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0816

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.0915

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0603

GnomAD3 exomes

AF:

0.105

AC:

26225

AN:

249050

Hom.:

2244

AF XY:

0.114

AC XY:

15363

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0757

Gnomad ASJ exome

AF:

0.0865

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.0920

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0835

GnomAD4 exome

AF:

0.0792

AC:

115616

AN:

1460450

Hom.:

7504

Cov.:

AF XY:

0.0860

AC XY:

62488

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0721

Gnomad4 ASJ exome

AF:

0.0854

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.0876

Gnomad4 NFE exome

AF:

0.0599

Gnomad4 OTH exome

AF:

0.0803

GnomAD4 genome

AF:

0.0662

AC:

10072

AN:

152144

Hom.:

587

Cov.:

AF XY:

0.0726

AC XY:

5401

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.0548

Gnomad4 ASJ

AF:

0.0816

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.0915

Gnomad4 NFE

AF:

0.0630

Gnomad4 OTH

AF:

0.0620

Alfa

AF:

0.0606

Hom.:

372

Bravo

AF:

0.0564

Asia WGS

AF:

0.232

AC:

806

AN:

3476

EpiCase

AF:

0.0627

EpiControl

AF:

0.0564

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

INTS2-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.92

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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