chr1-117402427-G-A

Position:

• chr1-117402427-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006699.5(MAN1A2):​c.544G>A​(p.Glu182Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,439,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MAN1A2 NM_006699.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

Genes affected

MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

MAN1A2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2183547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1A2	NM_006699.5	c.544G>A	p.Glu182Lys	missense_variant	2/13	ENST00000356554.7	NP_006690.1
MAN1A2	XM_006710302.4	c.544G>A	p.Glu182Lys	missense_variant	2/14		XP_006710365.1
MAN1A2	XM_011540536.4	c.544G>A	p.Glu182Lys	missense_variant	2/13		XP_011538838.1
MAN1A2	XM_017000115.2	c.544G>A	p.Glu182Lys	missense_variant	2/7		XP_016855604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A2	ENST00000356554.7	c.544G>A	p.Glu182Lys	missense_variant	2/13	1	NM_006699.5	ENSP00000348959.3
MAN1A2	ENST00000482811.1	n.544-12286G>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1439382 Hom.: 0 Cov.: 31 AF XY: 0.00000419 AC XY: 3 AN XY: 715466

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.0000260

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.544G>A (p.E182K) alteration is located in exon 2 (coding exon 2) of the MAN1A2 gene. This alteration results from a G to A substitution at nucleotide position 544, causing the glutamic acid (E) at amino acid position 182 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.042
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.16	T
Polyphen		0.0020	B
Vest4		0.28
MutPred		0.38		Gain of MoRF binding (P = 0.0046);
MVP		0.44
MPC		0.72
ClinPred		0.70	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.56

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: rs1409925555; hg19: chr1-117945049;