Variant 1-160945181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080878.3(ITLN2):c.937C>T(p.Arg313Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,605,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ITLN2
NM_080878.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

ITLN2 (HGNC:20599): (intelectin 2) Predicted to enable oligosaccharide binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ITLN2 links:

ENSG00000198358 (HGNC:):

ENSG00000198358 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36478376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITLN2	NM_080878.3 link	c.937C>T	p.Arg313Trp	missense_variant	8/8	ENST00000368029.4	NP_543154.1	Q8WWU7-1
ITLN2	XM_024453321.2 link	c.934C>T	p.Arg312Trp	missense_variant	8/8		XP_024309089.1
LOC101928372	NR_110695.1 link	n.846G>A		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITLN2	ENST00000368029.4 link	c.937C>T	p.Arg313Trp	missense_variant	8/8	1	NM_080878.3	ENSP00000357008.3	Q8WWU7-1
ENSG00000198358	ENST00000356006.3 link	n.846G>A		non_coding_transcript_exon_variant	5/6	1
ITLN2	ENST00000494442.1 link	n.797C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242506

Hom.:

AF XY:

0.0000380

AC XY:

AN XY:

131660

show subpopulations

Gnomad AFR exome

AF:

0.0000637

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

1453740

Hom.:

Cov.:

AF XY:

0.0000498

AC XY:

AN XY:

723366

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000433

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.0000968

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

The c.937C>T (p.R313W) alteration is located in exon 8 (coding exon 8) of the ITLN2 gene. This alteration results from a C to T substitution at nucleotide position 937, causing the arginine (R) at amino acid position 313 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.28

MVP

0.37

MPC

0.57

ClinPred

0.68

GERP RS

3.9

Varity_R

0.14

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over