rs1888727

Variant names:

• chr6-160093509-T-A
• rs1888727
• NM_000876.4:c.6656-2930T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160093509-T-A
• chr6-160093509-T-C
• chr6-160093509-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000876.4(IGF2R):​c.6656-2930T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• Publications: 10 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]

CHP1P2 (HGNC:54896): (CHP1 pseudogene 2) This locus on chromosome 6q25.3 represents a single-exon transcribed pseudogene of the multi-exon calcium binding protein P22 gene which resides on chromosome 15q13.3. This pseudogene is situated within an intron region of the insulin-like growth factor 2 receptor gene (IGF2R). [provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.6656-2930T>A		intron_variant	Intron 44 of 47	ENST00000356956.6	NP_000867.3
CHP1P2	NR_003288.2	n.428T>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.6656-2930T>A		intron_variant	Intron 44 of 47	1	NM_000876.4	ENSP00000349437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 424758 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 231636

African (AFR) AF: 0.00 AC: 0 AN: 11774

American (AMR) AF: 0.00 AC: 0 AN: 24724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11172

East Asian (EAS) AF: 0.00 AC: 0 AN: 25820

South Asian (SAS) AF: 0.00 AC: 0 AN: 52370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 241160

Other (OTH) AF: 0.00 AC: 0 AN: 22158

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1888727; hg19: chr6-160514541;