chr6-142382532-C-G

Variant names:

• chr6-142382532-C-G
• rs1040525
• NM_198569.3:c.1138+513C>G

Variant summary

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

The NM_198569.3(ADGRG6):​c.1138+513C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 151,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000026 (0 hom., cov: 33)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 9 publications found

Genes affected

ADGRG6 (HGNC:13841): (adhesion G protein-coupled receptor G6) This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person's stature. Multiple transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Mar 2009]

ADGRG6 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.1138+513C>G		intron_variant	Intron 5 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.1138+513C>G		intron_variant	Intron 5 of 24	1	NM_198569.3	ENSP00000356581.3
ADGRG6	ENST00000367608.6	c.1138+513C>G		intron_variant	Intron 5 of 23	1		ENSP00000356580.2
ADGRG6	ENST00000230173.10	c.1138+513C>G		intron_variant	Intron 5 of 25	1		ENSP00000230173.6
ADGRG6	ENST00000296932.13	c.1138+513C>G		intron_variant	Intron 5 of 24	1		ENSP00000296932.8

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151906 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151906 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74178

African (AFR) AF: 0.0000242 AC: 1 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 3699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.46
PhyloP100		0.068

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: rs1040525; hg19: chr6-142703669;