rs80239182

Variant names:

• chr2-219500030-G-A
• rs80239182
• NM_013335.4:c.40+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013335.4(GMPPA):​c.40+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,613,362 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (26 hom.)
• Consequence: GMPPA NM_013335.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.992
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-219500030-G-A is Benign according to our data. Variant chr2-219500030-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 382390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00908 (1383/152238) while in subpopulation AFR AF = 0.0312 (1295/41510). AF 95% confidence interval is 0.0298. There are 21 homozygotes in GnomAd4. There are 638 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013335.4. 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
	GMPPA	NM_013335.4	MANE Select	c.40+15G>A		intron	N/A	NP_037467.2
	GMPPA	NM_001438893.1		c.40+15G>A		intron	N/A	NP_001425822.1
	GMPPA	NM_001438894.1		c.40+15G>A		intron	N/A	NP_001425823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPPA	ENST00000313597.10	TSL:1 MANE Select	c.40+15G>A		intron	N/A	ENSP00000315925.6	Q96IJ6-1
	GMPPA	ENST00000358215.8	TSL:1	c.40+15G>A		intron	N/A	ENSP00000350949.3	Q96IJ6-1
	GMPPA	ENST00000950500.1		c.40+15G>A		intron	N/A	ENSP00000620559.1

Frequencies

GnomAD3 genomes AF: 0.00908 AC: 1382 AN: 152120 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00246 AC: 619 AN: 251420 AF XY: 0.00182

Gnomad AFR exome AF: 0.0325

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00101 AC: 1479 AN: 1461124 Hom.: 26 Cov.: 30 AF XY: 0.000876 AC XY: 637 AN XY: 726906

African (AFR) AF: 0.0345 AC: 1154 AN: 33462

American (AMR) AF: 0.00148 AC: 66 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.0000801 AC: 89 AN: 1111314

Other (OTH) AF: 0.00212 AC: 128 AN: 60376

GnomAD4 genome AF: 0.00908 AC: 1383 AN: 152238 Hom.: 21 Cov.: 32 AF XY: 0.00857 AC XY: 638 AN XY: 74434

African (AFR) AF: 0.0312 AC: 1295 AN: 41510

American (AMR) AF: 0.00366 AC: 56 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00489 Hom.: 7

Bravo AF: 0.0102

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Alacrima, achalasia, and intellectual disability syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.3
DANN	Benign	0.82
PhyloP100		-0.99
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism

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: rs80239182; hg19: chr2-220364752;