15-76340327-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_145805.3(ISL2):​c.563C>T​(p.Thr188Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T188R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ISL2
NM_145805.3 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.07
Variant links:
Genes affected
ISL2 (HGNC:18524): (ISL LIM homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in axonogenesis; neuron fate specification; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of neuron differentiation and neuron differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28987736).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISL2NM_145805.3 linkc.563C>T p.Thr188Met missense_variant Exon 4 of 6 ENST00000290759.9 NP_665804.1 Q96A47

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ISL2ENST00000290759.9 linkc.563C>T p.Thr188Met missense_variant Exon 4 of 6 1 NM_145805.3 ENSP00000290759.4 Q96A47
ISL2ENST00000558656.1 linkn.300C>T non_coding_transcript_exon_variant Exon 3 of 5 5 ENSP00000453837.1 H0YN25
ENSG00000259514ENST00000559539.1 linkn.338G>A non_coding_transcript_exon_variant Exon 2 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1459518
Hom.:
0
Cov.:
41
AF XY:
0.00000551
AC XY:
4
AN XY:
726068
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000337
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.29
T
MetaSVM
Uncertain
0.63
D
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.34
Sift
Benign
0.030
D
Sift4G
Benign
0.14
T
Polyphen
0.51
P
Vest4
0.30
MutPred
0.21
Gain of catalytic residue at V184 (P = 0.0265);
MVP
0.99
MPC
0.98
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.17
gMVP
0.35

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.

Other links and lift over

dbSNP: rs1290505874; hg19: chr15-76632668; API