17-61872412-AA-GT

Variant names:

• chr17-61872412-AA-GT
• NM_001351695.2:c.2630_2631delTTinsAC
• INTS2 p.Leu877His

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001351695.2(INTS2):​c.2630_2631delTTinsAC​(p.Leu877His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS2 NM_001351695.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.37
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.2630_2631delTTinsAC	p.Leu877His	missense	N/A	NP_001338624.2	J3KMZ7
	INTS2	NM_020748.4		c.2654_2655delTTinsAC	p.Leu885His	missense	N/A	NP_065799.2	Q9H0H0
	INTS2	NM_001330417.2		c.2630_2631delTTinsAC	p.Leu877His	missense	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.2630_2631delTTinsAC	p.Leu877His	missense	N/A	ENSP00000251334.6	J3KMZ7
	INTS2	ENST00000444766.7	TSL:1	c.2654_2655delTTinsAC	p.Leu885His	missense	N/A	ENSP00000414237.3	Q9H0H0
	INTS2	ENST00000647009.1		c.2630_2631delTTinsAC	p.Leu877His	missense	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
PhyloP100		8.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-59949773;