chr1-81943736-T-C

Position:

• chr1-81943736-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366006.2(ADGRL2):​c.1177T>C​(p.Ser393Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRL2 NM_001366006.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.1177T>C	p.Ser393Pro	missense_variant	6/24	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.1177T>C	p.Ser393Pro	missense_variant	6/24		NM_001366006.2	ENSP00000509478.1
ADGRL2	ENST00000370725.5	c.1165T>C	p.Ser389Pro	missense_variant	8/26	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.1165T>C	p.Ser389Pro	missense_variant	8/25	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.1165T>C	p.Ser389Pro	missense_variant	8/25	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.1165T>C	p.Ser389Pro	missense_variant	8/25	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.1165T>C	p.Ser389Pro	missense_variant	8/24	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.1177T>C	p.Ser393Pro	missense_variant	9/25	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.1165T>C (p.S389P) alteration is located in exon 5 (coding exon 4) of the ADGRL2 gene. This alteration results from a T to C substitution at nucleotide position 1165, causing the serine (S) at amino acid position 389 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;T;.;.;D;.;.;.;.;.;T;D
Eigen	Benign	-0.15
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;.;D;D;.;D;.;D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N;N;.;N
REVEL	Uncertain	0.38
Sift	Benign	0.26	T;T;T;T;T;T;T;T;T;T;.;T
Sift4G	Benign	0.43	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0030, 0.0050	.;.;.;.;.;.;B;B;B;B;.;.
Vest4		0.67
MutPred		0.53		.;Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);Gain of catalytic residue at S389 (P = 0.0668);
MVP		0.53
MPC		0.92
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.54
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-82409420;