chr16-57656280-G-A

Variant names:

• chr16-57656280-G-A
• rs587783650
• NM_201525.4:c.1063+9G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005682.7(ADGRG1):​c.1063+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRG1 NM_005682.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0910
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-57656280-G-A is Benign according to our data. Variant chr16-57656280-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2020433.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005682.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	NM_201525.4	MANE Select	c.1063+9G>A		intron	N/A	NP_958933.1
	ADGRG1	NM_001145771.3		c.1063+9G>A		intron	N/A	NP_001139243.1
	ADGRG1	NM_001370428.1		c.1063+9G>A		intron	N/A	NP_001357357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.1063+9G>A		intron	N/A	ENSP00000455351.2
	ADGRG1	ENST00000567835.5	TSL:1	c.1063+9G>A		intron	N/A	ENSP00000456794.1
	ADGRG1	ENST00000388813.9	TSL:1	c.1063+9G>A		intron	N/A	ENSP00000373465.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.39
PhyloP100		0.091

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

Other links and lift over

dbSNP: rs587783650; hg19: chr16-57690192;