17-7101587-G-A

Position:

• chr17-7101587-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001201352.2(ASGR2):​c.909C>T​(p.Gly303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,614,094 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (61 hom.)
• Consequence: ASGR2 NM_001201352.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.472

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-7101587-G-A is Benign according to our data. Variant chr17-7101587-G-A is described in ClinVar as [Benign]. Clinvar id is 786837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.472 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00312 (4556/1461786) while in subpopulation MID AF= 0.0283 (163/5768). AF 95% confidence interval is 0.0247. There are 61 homozygotes in gnomad4_exome. There are 2586 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASGR2	NM_001201352.2	c.909C>T	p.Gly303=	synonymous_variant	9/9	ENST00000691900.1	NP_001188281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASGR2	ENST00000691900.1	c.909C>T	p.Gly303=	synonymous_variant	9/9		NM_001201352.2	ENSP00000510808	A1
ASGR2	ENST00000355035.9	c.924C>T	p.Gly308=	synonymous_variant	9/9	1		ENSP00000347140	P4
ASGR2	ENST00000446679.6	c.867C>T	p.Gly289=	synonymous_variant	8/8	1		ENSP00000405844
ASGR2	ENST00000254850.11	c.852C>T	p.Gly284=	synonymous_variant	9/9	1		ENSP00000254850

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 544 AN: 152190 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00504 AC: 1266 AN: 251248 Hom.: 20 AF XY: 0.00578 AC XY: 785 AN XY: 135810

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.0138

Gnomad SAS exome AF: 0.0155

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00312 AC: 4556 AN: 1461786 Hom.: 61 Cov.: 31 AF XY: 0.00356 AC XY: 2586 AN XY: 727188

Gnomad4 AFR exome AF: 0.00329

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.0216

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000944

Gnomad4 OTH exome AF: 0.00532

GnomAD4 genome AF: 0.00356 AC: 542 AN: 152308 Hom.: 4 Cov.: 32 AF XY: 0.00381 AC XY: 284 AN XY: 74462

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00115

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00292 Hom.: 2

Bravo AF: 0.00386

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140278403; hg19: chr17-7004906;