rs12805507

Positions:

• chr11-22635318-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528582.5(GAS2):​c.-21+9505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,168 control chromosomes in the GnomAD database, including 2,101 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 0.15 (2101 hom., cov: 32)
• Consequence: GAS2 ENST00000528582.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS2	XM_011519972.4	c.-21+6925C>T		intron_variant			XP_011518274.1
GAS2	XM_047426745.1	c.-6052+6925C>T		intron_variant			XP_047282701.1
GAS2	XM_047426746.1	c.-21+6925C>T		intron_variant			XP_047282702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS2	ENST00000528582.5	c.-21+9505C>T		intron_variant		3		ENSP00000432584.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22815 AN: 152050 Hom.: 2100 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.150 AC: 22822 AN: 152168 Hom.: 2101 Cov.: 32 AF XY: 0.153 AC XY: 11350 AN XY: 74402

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0993

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.155

Alfa AF: 0.170 Hom.: 1142

Bravo AF: 0.133

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.4
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12805507; hg19: chr11-22656864;