1-81956516-A-T

Variant names:

• chr1-81956516-A-T
• rs3828121
• NM_001366006.2:c.2017+456A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366006.2(ADGRL2):​c.2017+456A>T 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 4 publications found

Genes affected

ADGRL2 (HGNC:18582): (adhesion G protein-coupled receptor L2) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors. The encoded protein participates in the regulation of exocytosis. The proprotein is thought to be further cleaved within a cysteine-rich G-protein-coupled receptor proteolysis site into two chains that are non-covalently bound at the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.2017+456A>T		intron_variant	Intron 11 of 23	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.2017+456A>T		intron_variant	Intron 11 of 23		NM_001366006.2	ENSP00000509478.1
ADGRL2	ENST00000370725.5	c.2005+456A>T		intron_variant	Intron 13 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.1966+456A>T		intron_variant	Intron 12 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.2005+456A>T		intron_variant	Intron 13 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.2005+456A>T		intron_variant	Intron 13 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.2005+456A>T		intron_variant	Intron 13 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.1780+456A>T		intron_variant	Intron 13 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.89

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: rs3828121; hg19: chr1-82422200;