3-127604987-C-T

Position:

chr3-127604987-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004526.4(MCM2):c.504C>T(p.Ile168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,613,788 control chromosomes in the GnomAD database, including 431,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35402 hom., cov: 33)

Exomes 𝑓: 0.73 ( 396478 hom. )

Consequence

MCM2
NM_004526.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

MCM2 (HGNC:6944): (minichromosome maintenance complex component 2) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7. Multiple alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been defined. [provided by RefSeq, Oct 2012]

MCM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 3-127604987-C-T is Benign according to our data. Variant chr3-127604987-C-T is described in ClinVar as [Benign]. Clinvar id is 508098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCM2	NM_004526.4 linkuse as main transcript	c.504C>T	p.Ile168=	synonymous_variant	4/16	ENST00000265056.12	NP_004517.2
MCM2	XM_024453531.2 linkuse as main transcript	c.477C>T	p.Ile159=	synonymous_variant	4/16		XP_024309299.1
MCM2	NR_073375.2 linkuse as main transcript	n.579C>T		non_coding_transcript_exon_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM2	ENST00000265056.12 linkuse as main transcript	c.504C>T	p.Ile168=	synonymous_variant	4/16	1	NM_004526.4	ENSP00000265056	P1

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102530

AN:

152018

Hom.:

35397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.691

GnomAD3 exomes

AF:

0.685

AC:

171734

AN:

250872

Hom.:

60110

AF XY:

0.689

AC XY:

93533

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.656

Gnomad SAS exome

AF:

0.574

Gnomad FIN exome

AF:

0.745

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.734

AC:

1072127

AN:

1461652

Hom.:

396478

Cov.:

AF XY:

0.730

AC XY:

531130

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.525

Gnomad4 AMR exome

AF:

0.564

Gnomad4 ASJ exome

AF:

0.745

Gnomad4 EAS exome

AF:

0.657

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.674

AC:

102565

AN:

152136

Hom.:

35402

Cov.:

AF XY:

0.671

AC XY:

49940

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.536

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.750

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.568

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.757

Gnomad4 OTH

AF:

0.687

Alfa

AF:

0.740

Hom.:

84975

Bravo

AF:

0.661

Asia WGS

AF:

0.611

AC:

2125

AN:

3478

EpiCase

AF:

0.767

EpiControl

AF:

0.770

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal dominant nonsyndromic hearing loss 70

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.3

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over