NM_173518.5:c.1831G>A

Variant names:

• chr8-66905287-G-A
• NM_173518.5:c.1831G>A

Variant summary

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

The NM_173518.5(MCMDC2):​c.1831G>A​(p.Val611Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,342,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MCMDC2 NM_173518.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.30
• 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]

SNHG6 (HGNC:32965): (small nucleolar RNA host gene 6)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1831G>A	p.Val611Met	missense	Exon 14 of 15	NP_775789.3
	MCMDC2	NM_001136160.2		c.1831G>A	p.Val611Met	missense	Exon 14 of 14	NP_001129632.1	B4DXX4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCMDC2	ENST00000422365.7	TSL:2 MANE Select	c.1831G>A	p.Val611Met	missense	Exon 14 of 15	ENSP00000413632.2	Q4G0Z9-1
	MCMDC2	ENST00000872356.1		c.1777G>A	p.Val593Met	missense	Exon 14 of 15	ENSP00000542415.1
	MCMDC2	ENST00000872355.1		c.1771G>A	p.Val591Met	missense	Exon 13 of 14	ENSP00000542414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1342738 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 660128

African (AFR) AF: 0.00 AC: 0 AN: 29768

American (AMR) AF: 0.00 AC: 0 AN: 30462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24040

East Asian (EAS) AF: 0.00 AC: 0 AN: 33218

South Asian (SAS) AF: 0.00 AC: 0 AN: 66120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00000286 AC: 3 AN: 1050528

Other (OTH) AF: 0.00 AC: 0 AN: 55434

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
PhyloP100		8.3
Varity_R		0.27
gMVP		0.56
Mutation Taster		=87/13	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-67817522;