22-21208901-G-A

Position:

• chr22-21208901-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NR_172944.1(GGT2P):​n.2088-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00965 in 1,358,952 control chromosomes in the GnomAD database, including 2,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (76 hom., cov: 14)
  • Exomes 𝑓: 0.0097 (2678 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGT2P NR_172944.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

Genes affected

ENSG00000290983 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-21208901-G-A is Benign according to our data. Variant chr22-21208901-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2678 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT2P	NR_172944.1	n.2088-5C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000290983	ENST00000697143.1	n.1894-5C>T		splice_region_variant, intron_variant
GGT2P	ENST00000697421.1	n.1307-5C>T		splice_region_variant, intron_variant
ENSG00000290983	ENST00000697422.1	n.2279-5C>T		splice_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 603 AN: 109940 Hom.: 76 Cov.: 14 FAILED QC

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00307

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00973

Gnomad OTH AF: 0.00285

GnomAD3 exomes AF: 0.00503 AC: 841 AN: 167096 Hom.: 125 AF XY: 0.00529 AC XY: 483 AN XY: 91374

Gnomad AFR exome AF: 0.00188

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.000254

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000866

Gnomad FIN exome AF: 0.00252

Gnomad NFE exome AF: 0.00931

Gnomad OTH exome AF: 0.00518

GnomAD4 exome AF: 0.00965 AC: 13114 AN: 1358952 Hom.: 2678 Cov.: 31 AF XY: 0.00922 AC XY: 6232 AN XY: 675892

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.0000407

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00116

Gnomad4 FIN exome AF: 0.00437

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.00867

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00548 AC: 603 AN: 110008 Hom.: 76 Cov.: 14 AF XY: 0.00509 AC XY: 267 AN XY: 52474

Gnomad4 AFR AF: 0.00186

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.00307

Gnomad4 NFE AF: 0.00973

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000170 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

GGT2P: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs200777496; hg19: chr22-21563190;