1-156727034-T-C

Position:

• chr1-156727034-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001370150.2(ISG20L2):​c.619A>G​(p.Asn207Asp) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ISG20L2 NM_001370150.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032325298).
• BP6: Variant 1-156727034-T-C is Benign according to our data. Variant chr1-156727034-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3530189.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISG20L2	NM_001370150.2	c.619A>G	p.Asn207Asp	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.619A>G	p.Asn207Asp	missense_variant	2/4	5	NM_001370150.2	ENSP00000357202.2
ISG20L2	ENST00000313146.10	c.619A>G	p.Asn207Asp	missense_variant	1/3	2		ENSP00000323424.6
ISG20L2	ENST00000496538.1	n.353A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.40
DEOGEN2	Benign	0.00039	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.73	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.049
Sift	Benign	0.75	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.0	B;B
Vest4		0.059
MutPred		0.32		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.19
MPC		0.33
ClinPred		0.027	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.55

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: chr1-156696826;