rs8191844

Variant names:

• chr6-160061897-C-G
• rs8191844
• NM_000876.4:c.3551C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-160061897-C-G
• chr6-160061897-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000876.4(IGF2R):​c.3551C>G​(p.Thr1184Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00174 in 1,614,126 control chromosomes in the GnomAD database, including 47 homozygotes. 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: 𝑓 0.0092 (26 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (21 hom.)
• Consequence: IGF2R NM_000876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0097438395).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00923 (1405/152240) while in subpopulation AFR AF = 0.0316 (1314/41548). AF 95% confidence interval is 0.0302. There are 26 homozygotes in GnomAd4. There are 665 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1405 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	NM_000876.4	MANE Select	c.3551C>G	p.Thr1184Ser	missense	Exon 25 of 48	NP_000867.3	P11717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	ENST00000356956.6	TSL:1 MANE Select	c.3551C>G	p.Thr1184Ser	missense	Exon 25 of 48	ENSP00000349437.1	P11717
	IGF2R	ENST00000650503.1		n.161C>G		non_coding_transcript_exon	Exon 2 of 24
	IGF2R	ENST00000676781.1		n.*1659C>G		non_coding_transcript_exon	Exon 26 of 49	ENSP00000504419.1	A0A7I2YQS7

Frequencies

GnomAD3 genomes AF: 0.00924 AC: 1405 AN: 152122 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00242 AC: 609 AN: 251458 AF XY: 0.00167

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000958 AC: 1401 AN: 1461886 Hom.: 21 Cov.: 32 AF XY: 0.000781 AC XY: 568 AN XY: 727246

African (AFR) AF: 0.0346 AC: 1159 AN: 33480

American (AMR) AF: 0.00179 AC: 80 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1112004

Other (OTH) AF: 0.00215 AC: 130 AN: 60396

GnomAD4 genome AF: 0.00923 AC: 1405 AN: 152240 Hom.: 26 Cov.: 33 AF XY: 0.00893 AC XY: 665 AN XY: 74454

African (AFR) AF: 0.0316 AC: 1314 AN: 41548

American (AMR) AF: 0.00386 AC: 59 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68008

Other (OTH) AF: 0.00997 AC: 21 AN: 2106

Alfa AF: 0.000455 Hom.: 1

Bravo AF: 0.0108

ESP6500AA AF: 0.0288 AC: 127

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00280 AC: 340

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0097	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Benign	0.064	T
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.53		Loss of sheet (P = 0.0457)
MVP		0.49
MPC		1.2
ClinPred		0.025	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.68
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8191844; hg19: chr6-160482929;