17-61873142-T-C

Variant names:

• chr17-61873142-T-C
• rs12451910
• NM_001351695.2:c.2583-682A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351695.2(INTS2):​c.2583-682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,078 control chromosomes in the GnomAD database, including 2,539 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 0.17 (2539 hom., cov: 32)
• Consequence: INTS2 NM_001351695.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS2	NM_001351695.2	c.2583-682A>G		intron_variant	Intron 19 of 24	ENST00000251334.7	NP_001338624.2
INTS2	NM_020748.4	c.2607-682A>G		intron_variant	Intron 19 of 24		NP_065799.2
INTS2	NM_001330417.2	c.2583-682A>G		intron_variant	Intron 19 of 24		NP_001317346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS2	ENST00000251334.7	c.2583-682A>G		intron_variant	Intron 19 of 24	2	NM_001351695.2	ENSP00000251334.6

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25178 AN: 151960 Hom.: 2534 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25200 AN: 152078 Hom.: 2539 Cov.: 32 AF XY: 0.172 AC XY: 12791 AN XY: 74328

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.175

Alfa AF: 0.160 Hom.: 2008

Bravo AF: 0.160

Asia WGS AF: 0.316 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs12451910; hg19: chr17-59950503;