chr11-22807366-G-A

Variant names:

• chr11-22807366-G-A
• rs16910194
• NM_001143830.3:c.724-4432G>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.724-4432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,134 control chromosomes in the GnomAD database, including 3,146 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 0.19 (3146 hom., cov: 33)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143830.3. 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
	GAS2	NM_001143830.3	MANE Select	c.724-4432G>A		intron	N/A	NP_001137302.1
	GAS2	NM_001391933.1		c.778-4432G>A		intron	N/A	NP_001378862.1
	GAS2	NM_001391934.1		c.724-4432G>A		intron	N/A	NP_001378863.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS2	ENST00000454584.7	TSL:1 MANE Select	c.724-4432G>A		intron	N/A	ENSP00000401145.2
	GAS2	ENST00000278187.7	TSL:1	c.724-4432G>A		intron	N/A	ENSP00000278187.3
	GAS2	ENST00000524701.5	TSL:2	n.*364-4432G>A		intron	N/A	ENSP00000432026.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28264 AN: 152016 Hom.: 3148 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.186 AC: 28281 AN: 152134 Hom.: 3146 Cov.: 33 AF XY: 0.182 AC XY: 13556 AN XY: 74374

African (AFR) AF: 0.307 AC: 12735 AN: 41480

American (AMR) AF: 0.124 AC: 1888 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3472

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5180

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10582

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10165 AN: 68000

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.163 Hom.: 2959

Bravo AF: 0.192

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.55
PhyloP100		-1.0
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: rs16910194; hg19: chr11-22828912;