chr15-90904279-C-T

Variant names:

• chr15-90904279-C-T
• rs2677743
• NM_006122.4:c.72C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006122.4(MAN2A2):​c.72C>T​(p.Leu24Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,614,154 control chromosomes in the GnomAD database, including 651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (348 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (303 hom.)
• Consequence: MAN2A2 NM_006122.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10
• Publications: 2 publications found

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]

MAN2A2 Gene-Disease associations (from GenCC):

• disorder of glycosylation

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 15-90904279-C-T is Benign according to our data. Variant chr15-90904279-C-T is described in ClinVar as Benign. ClinVar VariationId is 1227165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006122.4. 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
	MAN2A2	NM_006122.4	MANE Select	c.72C>T	p.Leu24Leu	synonymous	Exon 2 of 23	NP_006113.2	P49641-3
	MAN2A2	NM_001320977.2		c.72C>T	p.Leu24Leu	synonymous	Exon 3 of 25	NP_001307906.1
	MAN2A2	NR_135502.2		n.401C>T		non_coding_transcript_exon	Exon 2 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN2A2	ENST00000559717.6	TSL:2 MANE Select	c.72C>T	p.Leu24Leu	synonymous	Exon 2 of 23	ENSP00000452948.1	P49641-3
	MAN2A2	ENST00000360468.7	TSL:1	c.72C>T	p.Leu24Leu	synonymous	Exon 1 of 22	ENSP00000353655.3	P49641-3
	MAN2A2	ENST00000558161.5	TSL:1	n.72C>T		non_coding_transcript_exon	Exon 2 of 23	ENSP00000452631.1	A0A0C4DGL1

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5541 AN: 152166 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00930 AC: 2338 AN: 251422 AF XY: 0.00666

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00601

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00376 AC: 5492 AN: 1461870 Hom.: 303 Cov.: 31 AF XY: 0.00318 AC XY: 2310 AN XY: 727238

African (AFR) AF: 0.130 AC: 4359 AN: 33480

American (AMR) AF: 0.00684 AC: 306 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000244 AC: 271 AN: 1112000

Other (OTH) AF: 0.00813 AC: 491 AN: 60394

GnomAD4 genome AF: 0.0366 AC: 5568 AN: 152284 Hom.: 348 Cov.: 32 AF XY: 0.0356 AC XY: 2650 AN XY: 74458

African (AFR) AF: 0.126 AC: 5241 AN: 41530

American (AMR) AF: 0.0155 AC: 237 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68040

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.0157 Hom.: 96

Bravo AF: 0.0418

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.6
DANN	Benign	0.93
PhyloP100		1.1
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2677743; hg19: chr15-91447509;