2-219499740-TATTTGGG-T

Position:

• chr2-219499740-TATTTGGG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013335.4(GMPPA):​c.-20-215_-20-209del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00933 in 605,842 control chromosomes in the GnomAD database, including 245 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (54 hom.)
• Consequence: GMPPA NM_013335.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

Genes affected

GMPPA (HGNC:22923): (GDP-mannose pyrophosphorylase A) This gene is thought to encode a GDP-mannose pyrophosphorylase. This enzyme catalyzes the reaction which converts mannose-1-phosphate and GTP to GDP-mannose which is involved in the production of N-linked oligosaccharides. [provided by RefSeq, Jul 2008]

ASIC4-AS1 (HGNC:40960): (ASIC4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-219499740-TATTTGGG-T is Benign according to our data. Variant chr2-219499740-TATTTGGG-T is described in ClinVar as [Benign]. Clinvar id is 1224557.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMPPA	NM_013335.4	c.-20-215_-20-209del		intron_variant		ENST00000313597.10	NP_037467.2
ASIC4-AS1	XR_923921.2	n.391+16949_391+16955del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMPPA	ENST00000313597.10	c.-20-215_-20-209del		intron_variant		1	NM_013335.4	ENSP00000315925	P1
ASIC4-AS1	ENST00000429882.1	n.182+16949_182+16955del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4111 AN: 151994 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00338 AC: 1533 AN: 453730 Hom.: 54 AF XY: 0.00270 AC XY: 648 AN XY: 239564

Gnomad4 AFR exome AF: 0.0869

Gnomad4 AMR exome AF: 0.00645

Gnomad4 ASJ exome AF: 0.000508

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000403

Gnomad4 OTH exome AF: 0.00761

GnomAD4 genome AF: 0.0271 AC: 4118 AN: 152112 Hom.: 191 Cov.: 32 AF XY: 0.0259 AC XY: 1926 AN XY: 74386

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0254 Hom.: 6

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200922804; hg19: chr2-220364462;