NM_001351695.2:c.2933T>G

Variant names:

• chr17-61869834-A-C
• rs369347516
• NM_001351695.2:c.2933T>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001351695.2(INTS2):​c.2933T>G​(p.Leu978Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: INTS2 NM_001351695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.91
• Publications: 2 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29500324).

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.2933T>G	p.Leu978Trp	missense	Exon 21 of 25	NP_001338624.2	J3KMZ7
	INTS2	NM_020748.4		c.2957T>G	p.Leu986Trp	missense	Exon 21 of 25	NP_065799.2	Q9H0H0
	INTS2	NM_001330417.2		c.2933T>G	p.Leu978Trp	missense	Exon 21 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.2933T>G	p.Leu978Trp	missense	Exon 21 of 25	ENSP00000251334.6	J3KMZ7
	INTS2	ENST00000444766.7	TSL:1	c.2957T>G	p.Leu986Trp	missense	Exon 21 of 25	ENSP00000414237.3	Q9H0H0
	INTS2	ENST00000647009.1		c.2933T>G	p.Leu978Trp	missense	Exon 21 of 25	ENSP00000496407.1	J3KMZ7

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 12 AN: 249156 AF XY: 0.0000518

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 192 AN: 1461592 Hom.: 0 Cov.: 32 AF XY: 0.000118 AC XY: 86 AN XY: 727082

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000166 AC: 185 AN: 1111788

Other (OTH) AF: 0.0000994 AC: 6 AN: 60370

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74372

African (AFR) AF: 0.0000965 AC: 4 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

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

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.0000496 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.30
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Uncertain	0.012	D
Sift4G	Benign	0.097	T
Polyphen		0.99	D
Vest4		0.71
MVP		0.22
MPC		1.2
ClinPred		0.32	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.50
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs369347516; hg19: chr17-59947195;