rs2677744

Positions:

• chr15-90907211-G-A
• chr15-90907211-G-C

Variant summary

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

The NM_006122.4(MAN2A2):​c.1010-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,217,344 control chromosomes in the GnomAD database, including 140,358 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 0.55 (25605 hom., cov: 34)
  • Exomes 𝑓: 0.44 (114753 hom.)
• Consequence: MAN2A2 NM_006122.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

Genes affected

MAN2A2 (HGNC:6825): (mannosidase alpha class 2A member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in N-glycan processing and protein deglycosylation. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2A2	NM_006122.4	c.1010-98G>A		intron_variant		ENST00000559717.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2A2	ENST00000559717.6	c.1010-98G>A		intron_variant		2	NM_006122.4	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82858 AN: 152006 Hom.: 25558 Cov.: 34

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.437 AC: 465632 AN: 1065220 Hom.: 114753 Cov.: 14 AF XY: 0.439 AC XY: 235470 AN XY: 536596

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.994

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.545 AC: 82961 AN: 152124 Hom.: 25605 Cov.: 34 AF XY: 0.551 AC XY: 40976 AN XY: 74366

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.540

Alfa AF: 0.446 Hom.: 16794

Bravo AF: 0.579

Asia WGS AF: 0.822 AC: 2855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.054
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2677744; hg19: chr15-91450441;