Variant 17-7107142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001201352.2(ASGR2):c.506G>A(p.Arg169Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ASGR2
NM_001201352.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

ASGR2 (HGNC:743): (asialoglycoprotein receptor 2) This gene encodes a subunit of the asialoglycoprotein receptor. This receptor is a transmembrane protein that plays a critical role in serum glycoprotein homeostasis by mediating the endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues. The asialoglycoprotein receptor may facilitate hepatic infection by multiple viruses including hepatitis B, and is also a target for liver-specific drug delivery. The asialoglycoprotein receptor is a hetero-oligomeric protein composed of major and minor subunits, which are encoded by different genes. The protein encoded by this gene is the less abundant minor subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ASGR2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052146584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASGR2	NM_001201352.2 linkuse as main transcript	c.506G>A	p.Arg169Lys	missense_variant	7/9	ENST00000691900.1	NP_001188281.1	P07307Q7Z4G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASGR2	ENST00000691900.1 linkuse as main transcript	c.506G>A	p.Arg169Lys	missense_variant	7/9		NM_001201352.2	ENSP00000510808.1	Q7Z4G9
ASGR2	ENST00000355035.9 linkuse as main transcript	c.521G>A	p.Arg174Lys	missense_variant	7/9	1		ENSP00000347140.5	P07307-1
ASGR2	ENST00000446679.6 linkuse as main transcript	c.464G>A	p.Arg155Lys	missense_variant	6/8	1		ENSP00000405844.2	P07307-2
ASGR2	ENST00000254850.11 linkuse as main transcript	c.449G>A	p.Arg150Lys	missense_variant	7/9	1		ENSP00000254850.7	P07307-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.521G>A (p.R174K) alteration is located in exon 7 (coding exon 6) of the ASGR2 gene. This alteration results from a G to A substitution at nucleotide position 521, causing the arginine (R) at amino acid position 174 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.0

DANN

Benign

0.44

DEOGEN2

Benign

0.030

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.23

T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.41

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.74

T;T;T

Polyphen

0.016

B;B;B

Vest4

0.34

MutPred

0.51

Gain of methylation at R174 (P = 0.0116);.;.;

MVP

0.11

ClinPred

0.023

GERP RS

0.72

Varity_R

0.052

gMVP

0.38

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over