rs1266479

Positions:

• chr15-90921602-C-T

Variant summary

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

The NM_006122.4(MAN2A2):​c.*1815C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,180 control chromosomes in the GnomAD database, including 2,472 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 0.14 (2472 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: MAN2A2 NM_006122.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2A2	NM_006122.4	c.*1815C>T		3_prime_UTR_variant	23/23	ENST00000559717.6	NP_006113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN2A2	ENST00000559717.6	c.*1815C>T		3_prime_UTR_variant	23/23	2	NM_006122.4	ENSP00000452948	P1
MAN2A2	ENST00000360468.7	c.*1815C>T		3_prime_UTR_variant	22/22	1		ENSP00000353655	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21970 AN: 152056 Hom.: 2462 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.145 AC: 22013 AN: 152174 Hom.: 2472 Cov.: 33 AF XY: 0.143 AC XY: 10669 AN XY: 74406

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0952

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0949 Hom.: 970

Bravo AF: 0.149

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.5
DANN	Benign	0.75

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: rs1266479; hg19: chr15-91464832;