Variant 2-135844626-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005915.6(MCM6):c.2268C>T(p.Ile756Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,585,624 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 23 hom. )

Consequence

MCM6
NM_005915.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.955

Variant links:

Genes affected

MCM6 (HGNC:6949): (minichromosome maintenance complex component 6) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the 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. The MCM complex consisting of this protein and MCM2, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Single nucleotide polymorphisms in the intron regions of this gene are associated with differential transcriptional activation of the promoter of the neighboring lactase gene and, thereby, influence lactose intolerance in early adulthood. [provided by RefSeq, May 2012]

MCM6 links:

MCM6 (HGNC:):

MCM6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-135844626-G-A is Benign according to our data. Variant chr2-135844626-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.955 with no splicing effect.

BS2

High AC in GnomAd4 at 517 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM6	NM_005915.6 linkuse as main transcript	c.2268C>T	p.Ile756Ile	synonymous_variant	16/17	ENST00000264156.3	NP_005906.2	Q14566

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM6	ENST00000264156.3 linkuse as main transcript	c.2268C>T	p.Ile756Ile	synonymous_variant	16/17	1	NM_005915.6	ENSP00000264156.2		Q14566
MCM6	ENST00000492091.1 linkuse as main transcript	n.694C>T		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

517

AN:

151818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.0116

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00313

Gnomad FIN

AF:

0.00997

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00382

AC:

888

AN:

232360

Hom.:

AF XY:

0.00423

AC XY:

532

AN XY:

125762

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.0000598

Gnomad SAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.00798

Gnomad NFE exome

AF:

0.00449

Gnomad OTH exome

AF:

0.00401

GnomAD4 exome

AF:

0.00349

AC:

5006

AN:

1433688

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2634

AN XY:

712058

show subpopulations

Gnomad4 AFR exome

AF:

0.000432

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00964

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00281

Gnomad4 FIN exome

AF:

0.00823

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.00340

AC:

517

AN:

151936

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

245

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.0116

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00313

Gnomad4 FIN

AF:

0.00997

Gnomad4 NFE

AF:

0.00449

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00250

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	MCM6: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.8

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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