chr15-75356838-C-G

Position:

• chr15-75356838-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5 BP4 BS2_Supporting

The NM_006715.4(MAN2C1):​c.2612G>C​(p.Cys871Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,614,004 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (2 hom.)
• Consequence: MAN2C1 NM_006715.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.10

Genes affected

MAN2C1 (HGNC:6827): (mannosidase alpha class 2C member 1) Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

MAN2C1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP5: Variant 15-75356838-C-G is Pathogenic according to our data. Variant chr15-75356838-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1342928.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-75356838-C-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.12653661). . Strength limited to SUPPORTING due to the PP5.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2C1	NM_006715.4	c.2612G>C	p.Cys871Ser	missense_variant	22/26	ENST00000267978.10	NP_006706.2
NEIL1	NM_024608.4	c.*1804C>G		3_prime_UTR_variant	10/10	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN2C1	ENST00000267978.10	c.2612G>C	p.Cys871Ser	missense_variant	22/26	1	NM_006715.4	ENSP00000267978.4
NEIL1	ENST00000355059.9	c.*1804C>G		3_prime_UTR_variant	10/10	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000473 AC: 119 AN: 251328 Hom.: 0 AF XY: 0.000420 AC XY: 57 AN XY: 135872

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000959

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000907 AC: 1326 AN: 1461762 Hom.: 2 Cov.: 32 AF XY: 0.000866 AC XY: 630 AN XY: 727192

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74384

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000820 Hom.: 0

Bravo AF: 0.000416

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000486 AC: 59

EpiCase AF: 0.000763

EpiControl AF: 0.000771

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital disorder of deglycosylation 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Uncertain	0.61	.;.;.;D;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.54	N;.;.;N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.5	D;D;D;D;.
REVEL	Benign	0.24
Sift	Benign	0.44	T;T;T;T;.
Sift4G	Benign	0.82	T;T;T;T;T
Polyphen		0.024	.;.;.;B;.
Vest4		0.40
MutPred		0.77		Gain of disorder (P = 0.0066);.;.;Gain of disorder (P = 0.0066);.;
MVP		0.79
MPC		0.11
ClinPred		0.065	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.70

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: rs143755898; hg19: chr15-75649179;