17-64005224-C-G

Variant names:

• chr17-64005224-C-G
• rs758262793
• NM_001099789.2:c.211G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099789.2(ICAM2):​c.211G>C​(p.Glu71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E71K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ICAM2 NM_001099789.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.80
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07303944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM2	NM_001099789.2	MANE Select	c.211G>C	p.Glu71Gln	missense	Exon 3 of 5	NP_001093259.1	Q6FHE2
	ICAM2	NM_000873.4		c.211G>C	p.Glu71Gln	missense	Exon 2 of 4	NP_000864.2	Q6FHE2
	ICAM2	NM_001099786.2		c.211G>C	p.Glu71Gln	missense	Exon 4 of 6	NP_001093256.1	Q6FHE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM2	ENST00000579788.6	TSL:1 MANE Select	c.211G>C	p.Glu71Gln	missense	Exon 3 of 5	ENSP00000464665.1	P13598
	ICAM2	ENST00000449662.6	TSL:1	c.211G>C	p.Glu71Gln	missense	Exon 2 of 4	ENSP00000392634.2	P13598
	ICAM2	ENST00000852957.1		c.211G>C	p.Glu71Gln	missense	Exon 4 of 7	ENSP00000523016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0010
DANN	Benign	0.47
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		-5.8
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.017
Sift	Benign	0.25	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.054
MutPred		0.32		Loss of solvent accessibility (P = 0.0509)
MVP		0.14
MPC		0.26
ClinPred		0.11	T
GERP RS		-10
Varity_R		0.16
gMVP		0.27

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

Other links and lift over

dbSNP: rs758262793; hg19: chr17-62082584;