dbSNP rs201009410: ICAM2:p.Arg253Leu (chr17-64002817-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099789.2(ICAM2):c.758G>T(p.Arg253Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R253H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ICAM2
NM_001099789.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

ICAM2 links:

PRR29 (HGNC:25673): (proline rich 29)

PRR29 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09093827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM2	NM_001099789.2 link	c.758G>T	p.Arg253Leu	missense_variant	Exon 5 of 5	ENST00000579788.6	NP_001093259.1	P13598Q6FHE2
PRR29	NM_001164257.2 link	c.*1056C>A		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
ICAM2	ENST00000579788.6 link	c.758G>T	p.Arg253Leu	missense_variant	Exon 5 of 5	1	NM_001099789.2	ENSP00000464665.1		P13598
PRR29	ENST00000412177.6 link	c.*1056C>A		3_prime_UTR_variant	Exon 6 of 6	2	NM_001164257.2	ENSP00000400986.1		P0C7W0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000161

AC:

AN:

247992

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000411

AC:

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

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:

0.000151

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:

0.00000656

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

.;T;T;T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.81

T;T;.;.;.;T;.

M_CAP

Benign

0.0075

MetaRNN

Benign

0.091

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M;M;M;M;M

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.0

.;.;N;.;N;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.027

.;.;D;.;D;D;.

Sift4G

Uncertain

0.022

D;D;D;D;D;D;D

Polyphen

0.97

.;.;D;D;D;D;D

Vest4

0.28

MVP

0.31

MPC

0.83

ClinPred

0.41

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over