dbSNP rs773320366: MCMDC2:p.Leu305Val (chr8-66883834-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173518.5(MCMDC2):c.913C>G(p.Leu305Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L305F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MCMDC2
NM_173518.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

MCMDC2 (HGNC:26368): (minichromosome maintenance domain containing 2) Predicted to enable ATP binding activity and DNA binding activity. Predicted to be involved in double-strand break repair via break-induced replication. Predicted to act upstream of or within gamete generation and meiosis I cell cycle process. [provided by Alliance of Genome Resources, Apr 2022]

MCMDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3250878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCMDC2	NM_173518.5 link	c.913C>G	p.Leu305Val	missense_variant	Exon 9 of 15	ENST00000422365.7	NP_775789.3	Q4G0Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCMDC2	ENST00000422365.7 link	c.913C>G	p.Leu305Val	missense_variant	Exon 9 of 15	2	NM_173518.5	ENSP00000413632.2		Q4G0Z9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0035

.;T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.93

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.61, 0.73

.;P;P;P

Vest4

0.27

MutPred

0.68

Gain of methylation at K300 (P = 0.0669);Gain of methylation at K300 (P = 0.0669);Gain of methylation at K300 (P = 0.0669);Gain of methylation at K300 (P = 0.0669);

MVP

0.51

MPC

0.42

ClinPred

0.63

GERP RS

5.7

Varity_R

0.20

gMVP

0.52

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over