17-49042310-G-A

Position:

• chr17-49042310-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006546.4(IGF2BP1):​c.1010G>A​(p.Cys337Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF2BP1 NM_006546.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

Genes affected

IGF2BP1 (HGNC:28866): (insulin like growth factor 2 mRNA binding protein 1) This gene encodes a member of the insulin-like growth factor 2 mRNA-binding protein family. The protein encoded by this gene contains four K homology domains and two RNA recognition motifs. It functions by binding to the mRNAs of certain genes, including insulin-like growth factor 2, beta-actin and beta-transducin repeat-containing protein, and regulating their translation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP1	NM_006546.4	c.1010G>A	p.Cys337Tyr	missense_variant	9/15	ENST00000290341.8	NP_006537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP1	ENST00000290341.8	c.1010G>A	p.Cys337Tyr	missense_variant	9/15	1	NM_006546.4	ENSP00000290341.3
IGF2BP1	ENST00000431824.2	c.593G>A	p.Cys198Tyr	missense_variant	7/13	1		ENSP00000389135.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 2024

The c.1010G>A (p.C337Y) alteration is located in exon 9 (coding exon 9) of the IGF2BP1 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the cysteine (C) at amino acid position 337 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.016	D;T
Sift4G	Uncertain	0.021	D;D
Polyphen		0.95	P;.
Vest4		0.60
MutPred		0.44		Gain of helix (P = 0.0425);.;
MVP		0.40
MPC		2.5
ClinPred		0.97	D
GERP RS		5.6
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.83
gMVP		0.97

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-47119672;