rs12805507

Variant names:

• chr11-22635318-C-T
• rs12805507
• ENST00000528582.5:c.-21+9505C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.73).
• 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 rank	MANE	Protein	UniProt
GAS2	XM_011519972.4	c.-21+6925C>T		intron_variant	Intron 1 of 8		XP_011518274.1
GAS2	XM_047426745.1	c.-6052+6925C>T		intron_variant	Intron 1 of 9		XP_047282701.1
GAS2	XM_047426746.1	c.-21+6925C>T		intron_variant	Intron 1 of 7		XP_047282702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS2	ENST00000528582.5	c.-21+9505C>T		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.0611 AC: 2536 AN: 41538

American (AMR) AF: 0.0993 AC: 1518 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5166

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4824

European-Finnish (FIN) AF: 0.292 AC: 3096 AN: 10588

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13059 AN: 67978

Other (OTH) AF: 0.155 AC: 327 AN: 2114

Alfa AF: 0.170 Hom.: 1290

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
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs12805507; hg19: chr11-22656864;