17-61873142-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001351695.2(INTS2):​c.2583-682A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: INTS2 NM_001351695.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351695.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS2	NM_001351695.2	MANE Select	c.2583-682A>C		intron	N/A	NP_001338624.2	J3KMZ7
	INTS2	NM_020748.4		c.2607-682A>C		intron	N/A	NP_065799.2	Q9H0H0
	INTS2	NM_001330417.2		c.2583-682A>C		intron	N/A	NP_001317346.2	J3KMZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS2	ENST00000251334.7	TSL:2 MANE Select	c.2583-682A>C		intron	N/A	ENSP00000251334.6	J3KMZ7
	INTS2	ENST00000444766.7	TSL:1	c.2607-682A>C		intron	N/A	ENSP00000414237.3	Q9H0H0
	INTS2	ENST00000647009.1		c.2583-682A>C		intron	N/A	ENSP00000496407.1	J3KMZ7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.42
DANN	Benign	0.78
PhyloP100		-1.5

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

Other links and lift over

dbSNP: rs12451910; hg19: chr17-59950503;