Variant chrX-104658929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000372582.6(IL1RAPL2):c.16C>T(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,203,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 147 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 9 hem., cov: 24)

Exomes 𝑓: 0.00038 ( 0 hom. 138 hem. )

Consequence

IL1RAPL2
ENST00000372582.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

IL1RAPL2 (HGNC:5997): (interleukin 1 receptor accessory protein like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

IL1RAPL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075190067).

BP6

Variant X-104658929-C-T is Benign according to our data. Variant chrX-104658929-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2208312.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chrX-104658929-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RAPL2	NM_017416.2 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	2/11	ENST00000372582.6	NP_059112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RAPL2	ENST00000372582.6 linkuse as main transcript	c.16C>T	p.Leu6Phe	missense_variant	2/11	1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33978

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.0235

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:

0.00420

Gnomad NFE

AF:

0.000414

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.000337

AC:

AN:

178003

Hom.:

AF XY:

0.000397

AC XY:

AN XY:

62965

show subpopulations

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 SAS exome

AF:

0.0000573

Gnomad FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.000696

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.000376

AC:

410

AN:

1091644

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

138

AN XY:

357704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000753

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.000437

Gnomad4 OTH exome

AF:

0.000567

GnomAD4 genome

AF:

0.000403

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33978

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000414

Gnomad4 OTH

AF:

0.000665

Alfa

AF:

0.000492

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.16C>T (p.L6F) alteration is located in exon 2 (coding exon 1) of the IL1RAPL2 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the leucine (L) at amino acid position 6 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

IL1RAPL2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.033

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.40

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.47

REVEL

Benign

0.080

Sift

Benign

0.63

Sift4G

Benign

0.71

Polyphen

0.0010

Vest4

0.080

MVP

0.39

MPC

1.1

ClinPred

0.027

GERP RS

2.5

Varity_R

0.073

gMVP

0.69

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

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