NM_198569.3:c.2+179A>G

Variant names:

• chr6-142302510-A-G
• rs115240560
• NM_198569.3:c.2+179A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198569.3(ADGRG6):​c.2+179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 590,660 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (64 hom.)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000310391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-142302510-A-G is Benign according to our data. Variant chr6-142302510-A-G is described in ClinVar as Benign. ClinVar VariationId is 1270572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198569.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	NM_198569.3	MANE Select	c.2+179A>G		intron	N/A	NP_940971.2	Q86SQ4-3
	ADGRG6	NM_001032395.3		c.2+179A>G		intron	N/A	NP_001027567.2	Q86SQ4-4
	ADGRG6	NM_020455.6		c.2+179A>G		intron	N/A	NP_065188.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG6	ENST00000367609.8	TSL:1 MANE Select	c.2+179A>G		intron	N/A	ENSP00000356581.3	Q86SQ4-3
	ADGRG6	ENST00000367608.6	TSL:1	c.2+179A>G		intron	N/A	ENSP00000356580.2	Q86SQ4-4
	ADGRG6	ENST00000230173.10	TSL:1	c.2+179A>G		intron	N/A	ENSP00000230173.6	Q86SQ4-1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3410 AN: 152098 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.00942 AC: 4131 AN: 438444 Hom.: 64 Cov.: 6 AF XY: 0.00999 AC XY: 2287 AN XY: 228948

African (AFR) AF: 0.0542 AC: 609 AN: 11240

American (AMR) AF: 0.0130 AC: 183 AN: 14102

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 265 AN: 12716

East Asian (EAS) AF: 0.0000723 AC: 2 AN: 27670

South Asian (SAS) AF: 0.0224 AC: 802 AN: 35852

European-Finnish (FIN) AF: 0.000777 AC: 23 AN: 29612

Middle Eastern (MID) AF: 0.0379 AC: 96 AN: 2534

European-Non Finnish (NFE) AF: 0.00634 AC: 1773 AN: 279692

Other (OTH) AF: 0.0151 AC: 378 AN: 25026

GnomAD4 genome AF: 0.0224 AC: 3416 AN: 152216 Hom.: 84 Cov.: 32 AF XY: 0.0225 AC XY: 1676 AN XY: 74404

African (AFR) AF: 0.0583 AC: 2422 AN: 41528

American (AMR) AF: 0.0164 AC: 251 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4830

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00648 AC: 441 AN: 68014

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0124 Hom.: 11

Bravo AF: 0.0249

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.87
CADD	Benign	0.042
DANN	Benign	0.30
PhyloP100		-2.0
PromoterAI		0.061	Neutral
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: rs115240560; hg19: chr6-142623647;