17-7107899-C-G

Variant names:

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

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.346G>C​(p.Val116Leu) 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 1,461,510 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V116M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASGR2 NM_001201352.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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=0.053266525).

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>C	p.Val116Leu	missense	Exon 5 of 9	NP_001188281.1	Q7Z4G9
	ASGR2	NM_001181.4		c.361G>C	p.Val121Leu	missense	Exon 5 of 9	NP_001172.1	P07307
	ASGR2	NM_080912.3		c.361G>C	p.Val121Leu	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>C	p.Val116Leu	missense	Exon 5 of 9	ENSP00000510808.1	Q7Z4G9
	ASGR2	ENST00000355035.9	TSL:1	c.361G>C	p.Val121Leu	missense	Exon 5 of 9	ENSP00000347140.5	P07307-1
	ASGR2	ENST00000446679.6	TSL:1	c.304G>C	p.Val102Leu	missense	Exon 4 of 8	ENSP00000405844.2	P07307-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461510 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727068

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.019
DANN	Benign	0.14
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N
PhyloP100		-1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.013
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.24
MutPred		0.59		Loss of helix (P = 0.0626)
MVP		0.081
ClinPred		0.13	T
GERP RS		-2.4
Varity_R		0.032
gMVP		0.15

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: rs377144273; hg19: chr17-7011218;