Genetic Variant ISLR2:p.Ala239Thr (chr15-74133469-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020851.3(ISLR2):c.715G>A(p.Ala239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,612,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ISLR2
NM_020851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.223

Publications

0 publications found

Variant links:

Genes affected

ISLR2 (HGNC:29286): (immunoglobulin superfamily containing leucine rich repeat 2) Predicted to be involved in positive regulation of axon extension. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ISLR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.013357252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020851.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ISLR2	NM_020851.3	MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 3 of 3	NP_065902.1	Q6UXK2
ISLR2	NM_001130136.1		c.715G>A	p.Ala239Thr	missense	Exon 4 of 4	NP_001123608.1	Q6UXK2
ISLR2	NM_001130137.1		c.715G>A	p.Ala239Thr	missense	Exon 4 of 4	NP_001123609.1	Q6UXK2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ISLR2	ENST00000453268.3	TSL:1 MANE Select	c.715G>A	p.Ala239Thr	missense	Exon 3 of 3	ENSP00000411834.2	Q6UXK2
ISLR2	ENST00000361742.7	TSL:1	c.715G>A	p.Ala239Thr	missense	Exon 4 of 4	ENSP00000355402.3	Q6UXK2
ISLR2	ENST00000435464.5	TSL:2	c.715G>A	p.Ala239Thr	missense	Exon 4 of 4	ENSP00000411443.1	Q6UXK2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000531

AC:

AN:

244638

AF XY:

0.0000525

show subpopulations

Gnomad AFR exome

AF:

0.000778

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1460266

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33468

American (AMR)

AF:

0.0000224

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52178

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111778

Other (OTH)

AF:

0.0000994

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000250

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.000892

AC:

AN:

41472

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000307

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.000684

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000742

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

0.091

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.046

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.29

M_CAP

Benign

0.014

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.22

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.70

REVEL

Benign

0.035

Sift

Benign

0.40

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.026

MVP

0.048

ClinPred

0.0094

GERP RS

-2.1

Varity_R

0.054

gMVP

0.13

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over