NM_021957.4:c.1890+24_1890+25delTT

Variant names:

• chr12-21539232-CAA-C
• rs36023861
• NM_021957.4:c.1890+24_1890+25delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021957.4(GYS2):​c.1890+24_1890+25delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,273,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 2 publications found

Genes affected

GYS2 (HGNC:4707): (glycogen synthase 2) The protein encoded by this gene, liver glycogen synthase, catalyzes the rate-limiting step in the synthesis of glycogen - the transfer of a glucose molecule from UDP-glucose to a terminal branch of the glycogen molecule. Mutations in this gene cause glycogen storage disease type 0 (GSD-0) - a rare type of early childhood fasting hypoglycemia with decreased liver glycogen content. [provided by RefSeq, Dec 2009]

ENSG00000285854 (HGNC:):

SPX (HGNC:28139): (spexin hormone) The protein encoded by this gene is a hormone involved in modulation of cardiovascular and renal function. It has also been shown in rats to cause weight loss. Several transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYS2	NM_021957.4	c.1890+24_1890+25delTT		intron_variant	Intron 15 of 15	ENST00000261195.3	NP_068776.2
GYS2	XM_024448960.2	c.1890+24_1890+25delTT		intron_variant	Intron 15 of 16		XP_024304728.1
GYS2	XM_006719063.4	c.1659+24_1659+25delTT		intron_variant	Intron 14 of 14		XP_006719126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYS2	ENST00000261195.3	c.1890+24_1890+25delTT		intron_variant	Intron 15 of 15	1	NM_021957.4	ENSP00000261195.2
ENSG00000285854	ENST00000647960.1	n.*1892+24_*1892+25delTT		intron_variant	Intron 22 of 22			ENSP00000497202.1
SPX	ENST00000649016.1	n.2723_2724delAA		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000820 AC: 20 AN: 244042 AF XY: 0.000129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000600

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000229 AC: 257 AN: 1121540 Hom.: 0 AF XY: 0.000232 AC XY: 133 AN XY: 573590

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26774

American (AMR) AF: 0.0000463 AC: 2 AN: 43218

Ashkenazi Jewish (ASJ) AF: 0.0000838 AC: 2 AN: 23878

East Asian (EAS) AF: 0.00 AC: 0 AN: 38030

South Asian (SAS) AF: 0.000465 AC: 36 AN: 77398

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52776

Middle Eastern (MID) AF: 0.000681 AC: 3 AN: 4406

European-Non Finnish (NFE) AF: 0.000253 AC: 204 AN: 806056

Other (OTH) AF: 0.000184 AC: 9 AN: 49004

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151558 Hom.: 0 Cov.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 73992

African (AFR) AF: 0.0000243 AC: 1 AN: 41166

American (AMR) AF: 0.00 AC: 0 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000350 Hom.: 4211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs36023861; hg19: chr12-21692166;