6-160093509-T-G

Variant names:

• chr6-160093509-T-G
• rs1888727
• NM_000876.4:c.6656-2930T>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>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 424,758 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: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	NM_000876.4	MANE Select	c.6656-2930T>G		intron	N/A	NP_000867.3
	CHP1P2	NR_003288.2		n.428T>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	ENST00000356956.6	TSL:1 MANE Select	c.6656-2930T>G		intron	N/A	ENSP00000349437.1
	CHP1P2	ENST00000366273.3	TSL:6	n.87T>G		non_coding_transcript_exon	Exon 1 of 1
	IGF2R	ENST00000569097.2	TSL:6	n.428T>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000235 AC: 1 AN: 424758 Hom.: 0 Cov.: 0 AF XY: 0.00000432 AC XY: 1 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: 0.00000415 AC: 1 AN: 241160

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 37271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.4
DANN	Benign	0.66
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;