chr2-219499236-T-C

Variant names:

• chr2-219499236-T-C
• rs141582459
• ENST00000358215.8:c.-34T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001438895.1(GMPPA):​c.-34T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 152,324 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GMPPA NM_001438895.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-219499236-T-C is Benign according to our data. Variant chr2-219499236-T-C is described in ClinVar as Benign. ClinVar VariationId is 380067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.007 (1066/152324) while in subpopulation SAS AF = 0.0135 (65/4832). AF 95% confidence interval is 0.0108. There are 7 homozygotes in GnomAd4. There are 521 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438895.1. 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.-21+298T>C		intron	N/A	NP_037467.2
	GMPPA	NM_001438895.1		c.-34T>C		5_prime_UTR	Exon 1 of 12	NP_001425824.1
	GMPPA	NM_001374295.1		c.-39T>C		5_prime_UTR	Exon 1 of 13	NP_001361224.1	Q96IJ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPPA	ENST00000358215.8	TSL:1	c.-34T>C		5_prime_UTR	Exon 1 of 13	ENSP00000350949.3	Q96IJ6-1
	GMPPA	ENST00000313597.10	TSL:1 MANE Select	c.-21+298T>C		intron	N/A	ENSP00000315925.6	Q96IJ6-1
	GMPPA	ENST00000895889.1		c.-39T>C		5_prime_UTR	Exon 1 of 12	ENSP00000565948.1

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1066 AN: 152206 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00976

Gnomad OTH AF: 0.0101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 106 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 82

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.00700 AC: 1066 AN: 152324 Hom.: 7 Cov.: 32 AF XY: 0.00699 AC XY: 521 AN XY: 74492

African (AFR) AF: 0.00147 AC: 61 AN: 41568

American (AMR) AF: 0.00582 AC: 89 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4832

European-Finnish (FIN) AF: 0.0111 AC: 118 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00976 AC: 664 AN: 68028

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00812 Hom.: 3

Bravo AF: 0.00636

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.084
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs141582459; hg19: chr2-220363958;