16-57628885-AGAGTGT-AGAGTGTGAGTGT

Variant names:

• chr16-57628885-A-AGAGTGT
• rs879267570
• NM_201525.4:c.-36+91_-36+96dupAGTGTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_201525.4(ADGRG1):​c.-36+91_-36+96dupAGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000050 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• 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

ENSG00000261633 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-36+91_-36+96dupAGTGTG		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+91_-154+96dupAGTGTG		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9012_-154+9017dupAGTGTG		intron	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.-36+83_-36+84insGAGTGT		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8749_-154+8750insGAGTGT		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+57_-154+58insGAGTGT		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000501 AC: 33 AN: 659206 Hom.: 1 Cov.: 4 AF XY: 0.0000492 AC XY: 15 AN XY: 305140

African (AFR) AF: 0.00 AC: 0 AN: 11872

American (AMR) AF: 0.00 AC: 0 AN: 858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4188

East Asian (EAS) AF: 0.00 AC: 0 AN: 3190

South Asian (SAS) AF: 0.00 AC: 0 AN: 13522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1304

European-Non Finnish (NFE) AF: 0.0000548 AC: 33 AN: 602206

Other (OTH) AF: 0.00 AC: 0 AN: 21818

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

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: rs879267570; hg19: chr16-57662797;