17-64002817-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.758G>A​(p.Arg253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,778 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

ICAM2
NM_001099789.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.62
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]
PRR29 (HGNC:25673): (proline rich 29)

Genome browser will be placed here

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=0.015230387).
BP6
Variant 17-64002817-C-T is Benign according to our data. Variant chr17-64002817-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2592622.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.758G>A p.Arg253His missense_variant Exon 5 of 5 ENST00000579788.6 NP_001093259.1 P13598Q6FHE2
PRR29NM_001164257.2 linkc.*1056C>T 3_prime_UTR_variant Exon 6 of 6 ENST00000412177.6 NP_001157729.1 P0C7W0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ICAM2ENST00000579788.6 linkc.758G>A p.Arg253His missense_variant Exon 5 of 5 1 NM_001099789.2 ENSP00000464665.1 P13598
PRR29ENST00000412177.6 linkc.*1056C>T 3_prime_UTR_variant Exon 6 of 6 2 NM_001164257.2 ENSP00000400986.1 P0C7W0-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00769
Gnomad AMR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
247992
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134532
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000452
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000787
AC:
115
AN:
1461548
Hom.:
0
Cov.:
31
AF XY:
0.0000866
AC XY:
63
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000935
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Benign:1
Aug 04, 2023
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
0.082
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.0
DANN
Benign
0.96
DEOGEN2
Benign
0.020
.;T;T;T;T;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.76
T;T;.;.;.;T;.
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.015
T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.5
.;.;L;L;L;L;L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.5
.;.;N;.;N;N;.
REVEL
Benign
0.019
Sift
Benign
0.33
.;.;T;.;T;T;.
Sift4G
Benign
0.23
T;T;T;T;T;T;T
Polyphen
0.072
.;.;B;B;B;B;B
Vest4
0.10
MVP
0.17
MPC
0.33
ClinPred
0.053
T
GERP RS
-2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.037
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201009410; hg19: chr17-62080177; API