Genetic Variant NM_017416.2:c.32T>G (chrX-104658945-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017416.2(IL1RAPL2):c.32T>G(p.Val11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,206,142 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V11F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 2 hem. )

Consequence

IL1RAPL2
NM_017416.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 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.32T>G	p.Val11Gly	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.32T>G	p.Val11Gly	missense	Exon 2 of 11	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111909

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

178829

AF XY:

0.00

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:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000731

AC:

AN:

1094233

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

360119

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26231

American (AMR)

AF:

0.00

AC:

AN:

34688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19311

East Asian (EAS)

AF:

0.00

AC:

AN:

30126

South Asian (SAS)

AF:

0.00

AC:

AN:

53317

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4119

European-Non Finnish (NFE)

AF:

0.00000952

AC:

AN:

839969

Other (OTH)

AF:

0.00

AC:

AN:

45958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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

AF:

0.0000179

AC:

AN:

111909

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34095

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30817

American (AMR)

AF:

0.00

AC:

AN:

10515

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53172

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.24

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

PhyloP100

3.6

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.49

REVEL

Benign

0.14

Sift

Benign

0.039

Sift4G

Benign

0.17

Polyphen

0.57

Vest4

0.56

MVP

0.72

MPC

1.3

ClinPred

0.23

GERP RS

5.3

Varity_R

0.26

gMVP

0.64

Mutation Taster

=52/48

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