rs774182901

Variant names:

• chr8-66883927-C-A
• rs774182901
• NM_173518.5:c.1006C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-66883927-C-A
• chr8-66883927-C-G
• chr8-66883927-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173518.5(MCMDC2):​c.1006C>A​(p.Arg336Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R336H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MCMDC2 NM_173518.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03463173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173518.5. 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
	MCMDC2	NM_173518.5	MANE Select	c.1006C>A	p.Arg336Ser	missense	Exon 9 of 15	NP_775789.3
	MCMDC2	NM_001136160.2		c.1006C>A	p.Arg336Ser	missense	Exon 9 of 14	NP_001129632.1	B4DXX4
	MCMDC2	NM_001136161.2		c.1006C>A	p.Arg336Ser	missense	Exon 9 of 13	NP_001129633.1	Q4G0Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCMDC2	ENST00000422365.7	TSL:2 MANE Select	c.1006C>A	p.Arg336Ser	missense	Exon 9 of 15	ENSP00000413632.2	Q4G0Z9-1
	MCMDC2	ENST00000396592.7	TSL:1	c.1006C>A	p.Arg336Ser	missense	Exon 9 of 13	ENSP00000379837.3	Q4G0Z9-2
	MCMDC2	ENST00000492775.5	TSL:1	c.1006C>A	p.Arg336Ser	missense	Exon 9 of 9	ENSP00000428037.1	G3XAN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.5
DANN	Benign	0.85
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.079
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.0060
Sift	Benign	0.71	T
Sift4G	Benign	0.73	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.32		Gain of disorder (P = 0.0504)
MVP		0.067
MPC		0.081
ClinPred		0.026	T
GERP RS		-2.4
Varity_R		0.11
gMVP		0.30
Mutation Taster		=99/1	polymorphism

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: rs774182901; hg19: chr8-67796162;