17-64005137-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001099789.2(ICAM2):​c.298G>A​(p.Glu100Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ICAM2
NM_001099789.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31
Variant links:
Genes affected
ICAM2 (HGNC:5345): (intercellular adhesion molecule 2) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein may play a role in lymphocyte recirculation by blocking LFA-1-dependent cell adhesion. It mediates adhesive interactions important for antigen-specific immune response, NK-cell mediated clearance, lymphocyte recirculation, and other cellular interactions important for immune response and surveillance. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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=0.0125207305).
BP6
Variant 17-64005137-C-T is Benign according to our data. Variant chr17-64005137-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3107892.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ICAM2NM_001099789.2 linkc.298G>A p.Glu100Lys missense_variant Exon 3 of 5 ENST00000579788.6 NP_001093259.1 P13598Q6FHE2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ICAM2ENST00000579788.6 linkc.298G>A p.Glu100Lys missense_variant Exon 3 of 5 1 NM_001099789.2 ENSP00000464665.1 P13598

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251364
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000435
Gnomad SAS 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:
0.00000479
AC:
7
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 03, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
0.071
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
0.0050
DANN
Benign
0.67
DEOGEN2
Benign
0.0026
T;T;T;T;T;T;T;T;.
Eigen
Benign
-2.4
Eigen_PC
Benign
-2.5
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.51
T;.;.;.;T;.;T;T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.013
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
.;N;N;N;N;N;.;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.35
.;N;.;N;N;.;.;.;.
REVEL
Benign
0.036
Sift
Benign
1.0
.;T;.;T;T;.;.;.;.
Sift4G
Benign
0.91
T;T;T;T;T;T;.;.;.
Polyphen
0.0
.;B;B;B;B;B;.;.;.
Vest4
0.14
MutPred
0.39
.;Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);Gain of ubiquitination at E100 (P = 0.0247);
MVP
0.13
MPC
0.29
ClinPred
0.023
T
GERP RS
-11
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.052
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs768243019; hg19: chr17-62082497; COSMIC: COSV104556284; COSMIC: COSV104556284; API