dbSNP rs142906631: ISLR2:p.Ala325Glu (chr15-74133728-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020851.3(ISLR2):c.974C>A(p.Ala325Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A325V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ISLR2
NM_020851.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.741

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23990807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISLR2	NM_020851.3 link	c.974C>A	p.Ala325Glu	missense_variant	Exon 3 of 3	ENST00000453268.3	NP_065902.1	Q6UXK2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISLR2	ENST00000453268.3 link	c.974C>A	p.Ala325Glu	missense_variant	Exon 3 of 3	1	NM_020851.3	ENSP00000411834.2		Q6UXK2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000849

AC:

AN:

235554

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128036

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457340

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;T;T;T;T

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.49

.;.;T;.;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

N;N;N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.69

N;N;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.031

D;D;D;D;D

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.97

D;D;D;D;D

Vest4

0.43

MutPred

0.40

Loss of glycosylation at P330 (P = 0.1577);Loss of glycosylation at P330 (P = 0.1577);Loss of glycosylation at P330 (P = 0.1577);Loss of glycosylation at P330 (P = 0.1577);Loss of glycosylation at P330 (P = 0.1577);

MVP

0.25

ClinPred

0.31

GERP RS

2.7

Varity_R

0.26

gMVP

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over