chr11-22635318-C-T

Variant names:

• chr11-22635318-C-T
• rs12805507
• ENST00000867051.1:c.-21+6925C>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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528582.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS2	ENST00000867051.1		c.-21+6925C>T		intron	N/A	ENSP00000537110.1
	GAS2	ENST00000528582.5	TSL:3	c.-21+9505C>T		intron	N/A	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 v4.9

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;