ISLR2 p.Thr312Ser

Variant names:

• chr15-74133688-A-T
• rs1435695204
• NM_020851.3:c.934A>T
• ISLR2 p.Thr312Ser

Your query was ambiguous. Multiple possible variants found:

• chr15-74133688-A-T
• chr15-74133689-C-G
• chr15-74133688-ACC-TCT
• chr15-74133688-ACC-TCA
• chr15-74133688-ACC-TCG
• chr15-74133689-CC-GT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020851.3(ISLR2):​c.934A>T​(p.Thr312Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ISLR2 NM_020851.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11466774).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISLR2	NM_020851.3	MANE Select	c.934A>T	p.Thr312Ser	missense	Exon 3 of 3	NP_065902.1	Q6UXK2
	ISLR2	NM_001130136.1		c.934A>T	p.Thr312Ser	missense	Exon 4 of 4	NP_001123608.1	Q6UXK2
	ISLR2	NM_001130137.1		c.934A>T	p.Thr312Ser	missense	Exon 4 of 4	NP_001123609.1	Q6UXK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISLR2	ENST00000453268.3	TSL:1 MANE Select	c.934A>T	p.Thr312Ser	missense	Exon 3 of 3	ENSP00000411834.2	Q6UXK2
	ISLR2	ENST00000361742.7	TSL:1	c.934A>T	p.Thr312Ser	missense	Exon 4 of 4	ENSP00000355402.3	Q6UXK2
	ISLR2	ENST00000435464.5	TSL:2	c.934A>T	p.Thr312Ser	missense	Exon 4 of 4	ENSP00000411443.1	Q6UXK2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000866 AC: 2 AN: 230994 AF XY: 0.0000159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000611

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: 0.00000137 AC: 2 AN: 1455256 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723440

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.0000460 AC: 2 AN: 43520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.00 AC: 0 AN: 85480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108992

Other (OTH) AF: 0.00 AC: 0 AN: 60138

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.090	N
PhyloP100		4.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.038
Sift	Benign	0.33	T
Sift4G	Benign	0.29	T
Varity_R		0.085
gMVP		0.66

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1435695204;

hg19: chr15-74426029;