rs12293188

Variant names:

• chr11-22797828-G-A
• rs12293188
• NM_001143830.3:c.724-13970G>A

Variant summary

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

The NM_001143830.3(GAS2):​c.724-13970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,964 control chromosomes in the GnomAD database, including 3,887 homozygotes. 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 0.20 (3887 hom., cov: 32)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 7 publications found

Genes affected

GAS2 (HGNC:4167): (growth arrest specific 2) The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

GAS2 Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss, autosomal recessive 125

  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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS2	NM_001143830.3	c.724-13970G>A		intron_variant	Intron 7 of 7	ENST00000454584.7	NP_001137302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS2	ENST00000454584.7	c.724-13970G>A		intron_variant	Intron 7 of 7	1	NM_001143830.3	ENSP00000401145.2
GAS2	ENST00000278187.7	c.724-13970G>A		intron_variant	Intron 7 of 7	1		ENSP00000278187.3
GAS2	ENST00000524701.5	n.*364-13970G>A		intron_variant	Intron 8 of 8	2		ENSP00000432026.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30476 AN: 151846 Hom.: 3875 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.201 AC: 30518 AN: 151964 Hom.: 3887 Cov.: 32 AF XY: 0.197 AC XY: 14614 AN XY: 74302

African (AFR) AF: 0.354 AC: 14684 AN: 41448

American (AMR) AF: 0.134 AC: 2037 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 910 AN: 3466

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5186

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10580

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10190 AN: 67916

Other (OTH) AF: 0.197 AC: 416 AN: 2108

Alfa AF: 0.173 Hom.: 487

Bravo AF: 0.209

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.77
PhyloP100		-0.086
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: rs12293188; hg19: chr11-22819374;