chr1-156727250-G-C

Position:

• chr1-156727250-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370150.2(ISG20L2):​c.403C>G​(p.Arg135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ISG20L2 NM_001370150.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.215

Genes affected

ISG20L2 (HGNC:25745): (interferon stimulated exonuclease gene 20 like 2) This gene encodes a 3'-5' exoribonuclease that may be involved in the processing of the 12S pre-rRNA. Pseudogenes have been identified on chromosomes 6 and 11. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050030887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG20L2	NM_001370150.2	c.403C>G	p.Arg135Gly	missense_variant	2/4	ENST00000368219.2	NP_001357079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISG20L2	ENST00000368219.2	c.403C>G	p.Arg135Gly	missense_variant	2/4	5	NM_001370150.2	ENSP00000357202	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.403C>G (p.R135G) alteration is located in exon 1 (coding exon 1) of the ISG20L2 gene. This alteration results from a C to G substitution at nucleotide position 403, causing the arginine (R) at amino acid position 135 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.54
DANN	Benign	0.65
DEOGEN2	Benign	0.0038	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.56	N;N
REVEL	Benign	0.041
Sift	Benign	0.23	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0	B;B
Vest4		0.065
MutPred		0.29		Loss of MoRF binding (P = 0.0088);Loss of MoRF binding (P = 0.0088);
MVP		0.082
MPC		0.37
ClinPred		0.072	T
GERP RS		-0.90
Varity_R		0.25
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156697042;