rs202205145

Variant names:

• chr15-74133194-C-A
• rs202205145
• NM_020851.3:c.440C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-74133194-C-A
• chr15-74133194-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020851.3(ISLR2):​c.440C>A​(p.Pro147His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ISLR2 NM_020851.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775

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

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=0.13358346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISLR2	NM_020851.3	c.440C>A	p.Pro147His	missense_variant	Exon 3 of 3	ENST00000453268.3	NP_065902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISLR2	ENST00000453268.3	c.440C>A	p.Pro147His	missense_variant	Exon 3 of 3	1	NM_020851.3	ENSP00000411834.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460820 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726810

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T;T;T;T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.23	.;.;T;.;T;.
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;L;L;L;.;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.71	N;N;N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.094	T;T;T;T;T;T
Sift4G	Benign	0.11	T;T;T;T;T;T
Polyphen		0.15	B;B;B;B;.;B
Vest4		0.23
MutPred		0.31		Gain of catalytic residue at D148 (P = 0.0718);Gain of catalytic residue at D148 (P = 0.0718);Gain of catalytic residue at D148 (P = 0.0718);Gain of catalytic residue at D148 (P = 0.0718);Gain of catalytic residue at D148 (P = 0.0718);Gain of catalytic residue at D148 (P = 0.0718);
MVP		0.42
ClinPred		0.15	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.90

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

Other links and lift over

dbSNP: rs202205145; hg19: chr15-74425535;