chr17-7107899-C-T

Variant names:

• chr17-7107899-C-T
• rs377144273
• NM_001201352.2:c.346G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001201352.2(ASGR2):​c.346G>A​(p.Val116Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,636 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ASGR2 NM_001201352.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048068672).

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.346G>A	p.Val116Met	missense	Exon 5 of 9	NP_001188281.1	Q7Z4G9
	ASGR2	NM_001181.4		c.361G>A	p.Val121Met	missense	Exon 5 of 9	NP_001172.1	P07307
	ASGR2	NM_080912.3		c.361G>A	p.Val121Met	missense	Exon 5 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.346G>A	p.Val116Met	missense	Exon 5 of 9	ENSP00000510808.1	Q7Z4G9
	ASGR2	ENST00000355035.9	TSL:1	c.361G>A	p.Val121Met	missense	Exon 5 of 9	ENSP00000347140.5	P07307-1
	ASGR2	ENST00000446679.6	TSL:1	c.304G>A	p.Val102Met	missense	Exon 4 of 8	ENSP00000405844.2	P07307-2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000219 AC: 55 AN: 250960 AF XY: 0.000287

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000397

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000157 AC: 229 AN: 1461510 Hom.: 1 Cov.: 35 AF XY: 0.000169 AC XY: 123 AN XY: 727068

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53388

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.000174 AC: 194 AN: 1111958

Other (OTH) AF: 0.000182 AC: 11 AN: 60378

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74320

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000297 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000222 AC: 27

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000652

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	0.083
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.0
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.024
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Polyphen		0.39	B
Vest4		0.18
MVP		0.13
ClinPred		0.015	T
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.18
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs377144273; hg19: chr17-7011218;