dbSNP rs147061047: ISLR2:p.Asn85Ser (chr15-74133008-A-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_020851.3(ISLR2):c.254A>G(p.Asn85Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,613,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ISLR2
NM_020851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36913842).

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.254A>G	p.Asn85Ser	missense	Exon 3 of 3	NP_065902.1	Q6UXK2
ISLR2	NM_001130136.1		c.254A>G	p.Asn85Ser	missense	Exon 4 of 4	NP_001123608.1	Q6UXK2
ISLR2	NM_001130137.1		c.254A>G	p.Asn85Ser	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.254A>G	p.Asn85Ser	missense	Exon 3 of 3	ENSP00000411834.2	Q6UXK2
ISLR2	ENST00000361742.7	TSL:1	c.254A>G	p.Asn85Ser	missense	Exon 4 of 4	ENSP00000355402.3	Q6UXK2
ISLR2	ENST00000435464.5	TSL:2	c.254A>G	p.Asn85Ser	missense	Exon 4 of 4	ENSP00000411443.1	Q6UXK2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

248440

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.000377

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:

0.0000446

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461030

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

726864

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

1111858

Other (OTH)

AF:

0.0000166

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000105

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000194

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Uncertain

0.39

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

0.013

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.051

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.1

PhyloP100

5.0

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.27

Sift

Benign

0.086

Sift4G

Uncertain

0.052

Polyphen

0.092

Vest4

0.39

MVP

0.58

ClinPred

0.62

GERP RS

2.8

Varity_R

0.15

gMVP

0.92

Mutation Taster

=72/28

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