NM_173518.5:c.442A>C

Variant names:

• chr8-66877505-A-C
• rs374607726
• NM_173518.5:c.442A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173518.5(MCMDC2):​c.442A>C​(p.Arg148Arg) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MCMDC2 NM_173518.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.58
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

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.442A>C	p.Arg148Arg	synonymous	Exon 5 of 15	NP_775789.3
	MCMDC2	NM_001136160.2		c.442A>C	p.Arg148Arg	synonymous	Exon 5 of 14	NP_001129632.1	B4DXX4
	MCMDC2	NM_001136161.2		c.442A>C	p.Arg148Arg	synonymous	Exon 5 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.442A>C	p.Arg148Arg	synonymous	Exon 5 of 15	ENSP00000413632.2	Q4G0Z9-1
	MCMDC2	ENST00000396592.7	TSL:1	c.442A>C	p.Arg148Arg	synonymous	Exon 5 of 13	ENSP00000379837.3	Q4G0Z9-2
	MCMDC2	ENST00000492775.5	TSL:1	c.442A>C	p.Arg148Arg	synonymous	Exon 5 of 9	ENSP00000428037.1	G3XAN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455296 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723732

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.00 AC: 0 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.00 AC: 0 AN: 84310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110324

Other (OTH) AF: 0.0000166 AC: 1 AN: 60178

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		8.6

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: rs374607726; hg19: chr8-67789740;