rs998074

Variant names:

• chr6-160047351-T-A
• rs998074
• NM_000876.4:c.2229+15T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160047351-T-A
• chr6-160047351-T-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000876.4(IGF2R):​c.2229+15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000922 in 1,410,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 24 publications found

Genes affected

IGF2R (HGNC:5467): (insulin like growth factor 2 receptor) This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.2229+15T>A		intron_variant	Intron 16 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.2229+15T>A		intron_variant	Intron 16 of 47	1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000676781.1	n.*337+15T>A		intron_variant	Intron 17 of 48			ENSP00000504419.1
IGF2R	ENST00000677704.1	n.2229+15T>A		intron_variant	Intron 16 of 48			ENSP00000503314.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000922 AC: 13 AN: 1410348 Hom.: 0 Cov.: 31 AF XY: 0.00000716 AC XY: 5 AN XY: 697896

African (AFR) AF: 0.00 AC: 0 AN: 32098

American (AMR) AF: 0.00 AC: 0 AN: 39610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 79112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1090164

Other (OTH) AF: 0.0000171 AC: 1 AN: 58394

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 15268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.33
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs998074; hg19: chr6-160468383;