6-160105872-TCAAA-T

Variant names:

• chr6-160105872-TCAAA-T
• rs3832385
• NM_000876.4:c.*792_*795delACAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000876.4(IGF2R):​c.*792_*795delACAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,684 control chromosomes in the GnomAD database, including 5,581 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5566 hom., cov: 20)
  • Exomes 𝑓: 0.24 (15 hom.)
• Consequence: IGF2R NM_000876.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 3 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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.*792_*795delACAA		3_prime_UTR_variant	Exon 48 of 48	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.*792_*795delACAA		3_prime_UTR_variant	Exon 48 of 48	1	NM_000876.4	ENSP00000349437.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40629 AN: 151084 Hom.: 5560 Cov.: 20

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.239 AC: 115 AN: 482 Hom.: 15 AF XY: 0.243 AC XY: 73 AN XY: 300

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.235 AC: 99 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.239 AC: 11 AN: 46

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.269 AC: 40668 AN: 151202 Hom.: 5566 Cov.: 20 AF XY: 0.269 AC XY: 19831 AN XY: 73806

African (AFR) AF: 0.243 AC: 9987 AN: 41088

American (AMR) AF: 0.323 AC: 4912 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2193 AN: 5114

South Asian (SAS) AF: 0.268 AC: 1281 AN: 4776

European-Finnish (FIN) AF: 0.244 AC: 2542 AN: 10436

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18172 AN: 67844

Other (OTH) AF: 0.279 AC: 584 AN: 2090

Alfa AF: 0.268 Hom.: 674

Bravo AF: 0.280

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3832385; hg19: chr6-160526904; COSMIC: COSV63632917;