rs2015698

Positions:

• chr5-109809945-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002372.4(MAN2A1):​c.1944-7328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,840 control chromosomes in the GnomAD database, including 15,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15469 hom., cov: 32)
• Consequence: MAN2A1 NM_002372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

Genes affected

MAN2A1 (HGNC:6824): (mannosidase alpha class 2A member 1) This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2A1	NM_002372.4	c.1944-7328T>G		intron_variant		ENST00000261483.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2A1	ENST00000261483.5	c.1944-7328T>G		intron_variant		1	NM_002372.4	P1
MAN2A1	ENST00000502261.5	n.64-7328T>G		intron_variant, non_coding_transcript_variant		5
MAN2A1	ENST00000508043.1	n.102+5668T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66404 AN: 151722 Hom.: 15459 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66434 AN: 151840 Hom.: 15469 Cov.: 32 AF XY: 0.429 AC XY: 31860 AN XY: 74222

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.436

Alfa AF: 0.394 Hom.: 22476

Bravo AF: 0.456

Asia WGS AF: 0.230 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2015698; hg19: chr5-109145646;