rs11155242

Variant names:

• chr6-142370412-A-C
• rs11155242
• NM_198569.3:c.688A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198569.3(ADGRG6):​c.688A>C​(p.Lys230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,612,652 control chromosomes in the GnomAD database, including 30,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3068 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27425 hom.)
• Consequence: ADGRG6 NM_198569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 50 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015581548).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.688A>C	p.Lys230Gln	missense_variant	Exon 4 of 25	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.688A>C	p.Lys230Gln	missense_variant	Exon 4 of 25	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30259 AN: 152056 Hom.: 3061 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.186 AC: 46028 AN: 247820 AF XY: 0.189

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0943

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.191 AC: 278740 AN: 1460478 Hom.: 27425 Cov.: 33 AF XY: 0.192 AC XY: 139210 AN XY: 726510

African (AFR) AF: 0.215 AC: 7206 AN: 33450

American (AMR) AF: 0.162 AC: 7259 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4413 AN: 26122

East Asian (EAS) AF: 0.103 AC: 4079 AN: 39686

South Asian (SAS) AF: 0.227 AC: 19588 AN: 86194

European-Finnish (FIN) AF: 0.182 AC: 9733 AN: 53348

Middle Eastern (MID) AF: 0.154 AC: 888 AN: 5764

European-Non Finnish (NFE) AF: 0.193 AC: 214088 AN: 1110882

Other (OTH) AF: 0.190 AC: 11486 AN: 60332

GnomAD4 genome AF: 0.199 AC: 30307 AN: 152174 Hom.: 3068 Cov.: 32 AF XY: 0.199 AC XY: 14790 AN XY: 74408

African (AFR) AF: 0.219 AC: 9080 AN: 41504

American (AMR) AF: 0.201 AC: 3075 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.0951 AC: 493 AN: 5186

South Asian (SAS) AF: 0.233 AC: 1123 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1959 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13344 AN: 67986

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.195 Hom.: 11389

Bravo AF: 0.196

TwinsUK AF: 0.185 AC: 686

ALSPAC AF: 0.175 AC: 676

ESP6500AA AF: 0.208 AC: 761

ESP6500EA AF: 0.194 AC: 1586

ExAC AF: 0.187 AC: 22556

Asia WGS AF: 0.210 AC: 726 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.9
DANN	Benign	0.47
DEOGEN2	Benign	0.067	T;.;.;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.76	T;T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		1.1
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.080	N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.57	T;T;T;T;T
Sift4G	Benign	0.20	.;.;.;.;T
Polyphen		0.0080	B;B;B;B;B
Vest4		0.053
MPC		0.13
ClinPred		0.0071	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs11155242; hg19: chr6-142691549; COSMIC: COSV51588591; COSMIC: COSV51588591;