17-61867887-C-T

Variant names:

• chr17-61867887-C-T
• rs772400600
• NM_001351695.2:c.3367G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351695.2(INTS2):​c.3367G>A​(p.Val1123Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000509 in 1,610,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: INTS2 NM_001351695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1338507).

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.3367G>A	p.Val1123Ile	missense	Exon 24 of 25	NP_001338624.2	J3KMZ7
	INTS2	NM_020748.4		c.3391G>A	p.Val1131Ile	missense	Exon 24 of 25	NP_065799.2	Q9H0H0
	INTS2	NM_001330417.2		c.3367G>A	p.Val1123Ile	missense	Exon 24 of 25	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.3367G>A	p.Val1123Ile	missense	Exon 24 of 25	ENSP00000251334.6	J3KMZ7
	INTS2	ENST00000444766.7	TSL:1	c.3391G>A	p.Val1131Ile	missense	Exon 24 of 25	ENSP00000414237.3	Q9H0H0
	INTS2	ENST00000647009.1		c.3367G>A	p.Val1123Ile	missense	Exon 24 of 25	ENSP00000496407.1	J3KMZ7

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000611 AC: 15 AN: 245664 AF XY: 0.0000526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000326

Gnomad NFE exome AF: 0.0000715

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000473 AC: 69 AN: 1458484 Hom.: 1 Cov.: 31 AF XY: 0.0000510 AC XY: 37 AN XY: 725332

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85224

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1110932

Other (OTH) AF: 0.0000332 AC: 2 AN: 60248

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000414 AC: 5

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.0096
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L
PhyloP100		5.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.034
Sift	Benign	0.51	T
Sift4G	Benign	0.55	T
Polyphen		0.0080	B
Vest4		0.44
MVP		0.19
MPC		0.33
ClinPred		0.13	T
GERP RS		4.4
Varity_R		0.20
gMVP		0.39
Mutation Taster		=85/15	polymorphism

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: rs772400600; hg19: chr17-59945248; COSMIC: COSV52003709; COSMIC: COSV52003709;