chr17-7107142-C-T

Variant names:

• chr17-7107142-C-T
• NM_001201352.2:c.506G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

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]

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 (MetaRNN=0.052146584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201352.2. 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
	ASGR2	NM_001201352.2	MANE Select	c.506G>A	p.Arg169Lys	missense	Exon 7 of 9	NP_001188281.1	Q7Z4G9
	ASGR2	NM_001181.4		c.521G>A	p.Arg174Lys	missense	Exon 7 of 9	NP_001172.1	P07307
	ASGR2	NM_080912.3		c.521G>A	p.Arg174Lys	missense	Exon 7 of 9	NP_550434.1	P07307

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASGR2	ENST00000691900.1	MANE Select	c.506G>A	p.Arg169Lys	missense	Exon 7 of 9	ENSP00000510808.1	Q7Z4G9
	ASGR2	ENST00000355035.9	TSL:1	c.521G>A	p.Arg174Lys	missense	Exon 7 of 9	ENSP00000347140.5	P07307-1
	ASGR2	ENST00000446679.6	TSL:1	c.464G>A	p.Arg155Lys	missense	Exon 6 of 8	ENSP00000405844.2	P07307-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.32	T
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	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.41	N
PhyloP100		-1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.031
Sift	Benign	0.58	T
Sift4G	Benign	0.74	T
Polyphen		0.016	B
Vest4		0.34
MutPred		0.51		Gain of methylation at R174 (P = 0.0116)
MVP		0.11
ClinPred		0.023	T
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

Other links and lift over

hg19: chr17-7010461; COSMIC: COSV54691308; COSMIC: COSV54691308;