rs1251742846

Variant names:

• chr17-64003947-T-C
• rs1251742846
• NM_001099789.2:c.346A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-64003947-T-C
• chr17-64003947-T-A
• chr17-64003947-T-G

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.346A>G​(p.Ile116Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ICAM2 NM_001099789.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.612
• 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]

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

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=0.08560616).

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.346A>G	p.Ile116Val	missense	Exon 4 of 5	NP_001093259.1	Q6FHE2
	PRR29	NM_001164257.2	MANE Select	c.*2186T>C		3_prime_UTR	Exon 6 of 6	NP_001157729.1	P0C7W0-1
	ICAM2	NM_000873.4		c.346A>G	p.Ile116Val	missense	Exon 3 of 4	NP_000864.2	Q6FHE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM2	ENST00000579788.6	TSL:1 MANE Select	c.346A>G	p.Ile116Val	missense	Exon 4 of 5	ENSP00000464665.1	P13598
	ICAM2	ENST00000449662.6	TSL:1	c.346A>G	p.Ile116Val	missense	Exon 3 of 4	ENSP00000392634.2	P13598
	PRR29	ENST00000412177.6	TSL:2 MANE Select	c.*2186T>C		3_prime_UTR	Exon 6 of 6	ENSP00000400986.1	P0C7W0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246248 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.45
DANN	Benign	0.34
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.99	L
PhyloP100		-0.61
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.020
Sift	Benign	0.61	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.49		Gain of catalytic residue at I116 (P = 0.1863)
MVP		0.072
MPC		0.22
ClinPred		0.023	T
GERP RS		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.044
gMVP		0.10

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

Other links and lift over

dbSNP: rs1251742846; hg19: chr17-62081307;