Genetic Variant NM_017416.2:c.22G>A (chrX-104658935-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017416.2(IL1RAPL2):c.22G>A(p.Ala8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,092,293 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 5 hem. )

Consequence

IL1RAPL2
NM_017416.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07676026).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017416.2. 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
	IL1RAPL2	NM_017416.2	MANE Select	c.22G>A	p.Ala8Thr	missense	Exon 2 of 11	NP_059112.1	Q9NP60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.22G>A	p.Ala8Thr	missense	Exon 2 of 11	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000562

AC:

AN:

177897

AF XY:

0.0000159

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1092293

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

358355

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26146

American (AMR)

AF:

0.00

AC:

AN:

34511

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19279

East Asian (EAS)

AF:

0.00

AC:

AN:

30078

South Asian (SAS)

AF:

0.00

AC:

AN:

52931

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40509

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

838814

Other (OTH)

AF:

0.0000218

AC:

AN:

45913

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.038

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.44

M_CAP

Benign

0.0051

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PhyloP100

2.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.15

REVEL

Benign

0.051

Sift

Benign

0.78

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.26

MutPred

0.49

Gain of sheet (P = 0.0028)

MVP

0.34

MPC

0.97

ClinPred

0.034

GERP RS

1.3

Varity_R

0.067

gMVP

0.66

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over