rs753765

Variant names:

• chr17-61891639-T-C
• rs753765
• NM_001351695.2:c.1749A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_020748.4(INTS2):​c.1773A>G​(p.Gln591Gln) 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_020748.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.314
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020748.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS2	NM_001351695.2	MANE Select	c.1749A>G	p.Gln583Gln	synonymous	Exon 14 of 25	NP_001338624.2
	INTS2	NM_020748.4		c.1773A>G	p.Gln591Gln	synonymous	Exon 14 of 25	NP_065799.2
	INTS2	NM_001330417.2		c.1749A>G	p.Gln583Gln	synonymous	Exon 14 of 25	NP_001317346.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS2	ENST00000251334.7	TSL:2 MANE Select	c.1749A>G	p.Gln583Gln	synonymous	Exon 14 of 25	ENSP00000251334.6
	INTS2	ENST00000444766.7	TSL:1	c.1773A>G	p.Gln591Gln	synonymous	Exon 14 of 25	ENSP00000414237.3
	INTS2	ENST00000647009.1		c.1749A>G	p.Gln583Gln	synonymous	Exon 14 of 25	ENSP00000496407.1

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10065 AN: 152026 Hom.: 587 Cov.: 31

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

GnomAD2 exomes AF: 0.105 AC: 26225 AN: 249050 AF XY: 0.114

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 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.: 30 AF XY: 0.0860 AC XY: 62488 AN XY: 726592

African (AFR) AF: 0.0154 AC: 514 AN: 33462

American (AMR) AF: 0.0721 AC: 3221 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 2230 AN: 26120

East Asian (EAS) AF: 0.226 AC: 8945 AN: 39640

South Asian (SAS) AF: 0.281 AC: 24224 AN: 86166

European-Finnish (FIN) AF: 0.0876 AC: 4676 AN: 53394

Middle Eastern (MID) AF: 0.0791 AC: 456 AN: 5762

European-Non Finnish (NFE) AF: 0.0599 AC: 66508 AN: 1110888

Other (OTH) AF: 0.0803 AC: 4842 AN: 60316

GnomAD4 genome AF: 0.0662 AC: 10072 AN: 152144 Hom.: 587 Cov.: 31 AF XY: 0.0726 AC XY: 5401 AN XY: 74358

African (AFR) AF: 0.0176 AC: 731 AN: 41532

American (AMR) AF: 0.0548 AC: 837 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5158

South Asian (SAS) AF: 0.301 AC: 1450 AN: 4824

European-Finnish (FIN) AF: 0.0915 AC: 967 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0630 AC: 4286 AN: 68000

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0613 Hom.: 563

Bravo AF: 0.0564

Asia WGS AF: 0.232 AC: 806 AN: 3476

EpiCase AF: 0.0627

EpiControl AF: 0.0564

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	INTS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.92
DANN	Benign	0.46
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs753765; hg19: chr17-59969000; COSMIC: COSV52150946;