Variant 15-60431994-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024611.6(ICE2):c.2511-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,380,742 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 5 hom. )

Consequence

ICE2
NM_024611.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001439

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.463

Variant links:

Genes affected

ICE2 (HGNC:29885): (interactor of little elongation complex ELL subunit 2) This gene encodes a protein component of the little elongation complex (LEC), which plays a role in small nuclear RNA (snRNA) transcription. The LEC regulates snRNA transcription by enhancing both RNA Polymerase II occupancy and transcriptional elongation. The encoded protein and other LEC components have been shown to localize to Cajal bodies, which are sites of ribonucleoprotein (RNP) complex assembly. Pseudogenes of this gene have been identified on chromosomes 3 and 4. [provided by RefSeq, May 2017]

ICE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-60431994-A-G is Benign according to our data. Variant chr15-60431994-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3043172.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICE2	NM_024611.6 linkuse as main transcript	c.2511-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261520.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ICE2	ENST00000261520.9 linkuse as main transcript	c.2511-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_024611.6	P1	Q659A1-1
ICE2	ENST00000558181.5 linkuse as main transcript	c.*2129-10T>C	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1			Q659A1-2
ICE2	ENST00000558121.5 linkuse as main transcript	n.742-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
ICE2	ENST00000561124.1 linkuse as main transcript	n.124-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

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:

0.00497

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000551

AC:

130

AN:

235968

Hom.:

AF XY:

0.000745

AC XY:

AN XY:

127576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000351

GnomAD4 exome

AF:

0.000282

AC:

346

AN:

1228466

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

257

AN XY:

615722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00439

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000218

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000164

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ICE2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over