16-57655473-CG-GT

Variant names:

• chr16-57655473-CG-GT
• rs1057517931
• NM_201525.4:c.843_844delCGinsGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_201525.4(ADGRG1):​c.843_844delCGinsGT​(p.SerGly281ArgTrp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. SG281RR) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRG1 NM_201525.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.262
• Publications: 0 publications found

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. 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
	ADGRG1	NM_201525.4	MANE Select	c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.843_844delCGinsGT	p.SerGly281ArgTrp	missense	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs1057517931; hg19: chr16-57689385;