15-60442498-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_024611.6(ICE2):c.2343T>C(p.Tyr781=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,589,462 control chromosomes in the GnomAD database, including 276,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (22662 hom., cov: 32)
  • Exomes 𝑓: 0.59 (253383 hom.)
• Consequence: ICE2 NM_024611.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.959

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-60442498-A-G is Benign according to our data. Variant chr15-60442498-A-G is described in ClinVar as [Benign]. Clinvar id is 1222476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.959 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICE2	NM_024611.6	c.2343T>C	p.Tyr781=	synonymous_variant	12/16	ENST00000261520.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICE2	ENST00000261520.9	c.2343T>C	p.Tyr781=	synonymous_variant	12/16	1	NM_024611.6	P1
ICE2	ENST00000558121.5	n.574T>C		non_coding_transcript_exon_variant	1/5	1
ICE2	ENST00000561328.1	n.1223T>C		non_coding_transcript_exon_variant	3/3	1
ICE2	ENST00000558181.5	c.*1961T>C		3_prime_UTR_variant, NMD_transcript_variant	12/16	1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79250 AN: 151962 Hom.: 22640 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.611 AC: 139840 AN: 228984 Hom.: 44979 AF XY: 0.616 AC XY: 76424 AN XY: 124142

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.825

Gnomad SAS exome AF: 0.772

Gnomad FIN exome AF: 0.716

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.586 AC: 842934 AN: 1437382 Hom.: 253383 Cov.: 31 AF XY: 0.591 AC XY: 422652 AN XY: 714760

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.712

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.521 AC: 79293 AN: 152080 Hom.: 22662 Cov.: 32 AF XY: 0.535 AC XY: 39757 AN XY: 74354

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.508

Alfa AF: 0.508 Hom.: 8098

Bravo AF: 0.499

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 05, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.37
Dann	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1063100; hg19: chr15-60734697;