11-22677466-G-C

Variant names:

• chr11-22677466-G-C
• rs10500940
• NM_001143830.3:c.145+2452G>C

Variant summary

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

The NM_001143830.3(GAS2):​c.145+2452G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 152,296 control chromosomes in the GnomAD database, including 74 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 0.025 (74 hom., cov: 32)
• Consequence: GAS2 NM_001143830.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0604 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS2	NM_001143830.3	MANE Select	c.145+2452G>C		intron	N/A	NP_001137302.1
	GAS2	NM_001391933.1		c.145+2452G>C		intron	N/A	NP_001378862.1
	GAS2	NM_001391934.1		c.145+2452G>C		intron	N/A	NP_001378863.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS2	ENST00000454584.7	TSL:1 MANE Select	c.145+2452G>C		intron	N/A	ENSP00000401145.2
	GAS2	ENST00000278187.7	TSL:1	c.145+2452G>C		intron	N/A	ENSP00000278187.3
	GAS2	ENST00000867053.1		c.145+2452G>C		intron	N/A	ENSP00000537112.1

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3770 AN: 152178 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0248 AC: 3777 AN: 152296 Hom.: 74 Cov.: 32 AF XY: 0.0249 AC XY: 1851 AN XY: 74460

African (AFR) AF: 0.00700 AC: 291 AN: 41576

American (AMR) AF: 0.0536 AC: 820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.0662 AC: 343 AN: 5184

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.0236 AC: 251 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1949 AN: 68012

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.00719 Hom.: 1

Bravo AF: 0.0276

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.64
PhyloP100		-1.8
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: rs10500940; hg19: chr11-22699012;