rs112645348

Variant names:

• chr8-66890892-C-A
• rs112645348
• NM_173518.5:c.1101C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-66890892-C-A
• chr8-66890892-C-G
• chr8-66890892-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_173518.5(MCMDC2):​c.1101C>A​(p.Val367Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000838 in 1,611,698 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (9 hom.)
• Consequence: MCMDC2 NM_173518.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0510
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 8-66890892-C-A is Benign according to our data. Variant chr8-66890892-C-A is described in ClinVar as Benign. ClinVar VariationId is 789601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000463 (676/1459572) while in subpopulation AFR AF = 0.0165 (552/33364). AF 95% confidence interval is 0.0154. There are 9 homozygotes in GnomAdExome4. There are 291 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.1101C>A	p.Val367Val	synonymous	Exon 10 of 15	NP_775789.3
	MCMDC2	NM_001136160.2		c.1101C>A	p.Val367Val	synonymous	Exon 10 of 14	NP_001129632.1	B4DXX4
	MCMDC2	NM_001136161.2		c.1101C>A	p.Val367Val	synonymous	Exon 10 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.1101C>A	p.Val367Val	synonymous	Exon 10 of 15	ENSP00000413632.2	Q4G0Z9-1
	MCMDC2	ENST00000396592.7	TSL:1	c.1101C>A	p.Val367Val	synonymous	Exon 10 of 13	ENSP00000379837.3	Q4G0Z9-2
	MCMDC2	ENST00000872356.1		c.1047C>A	p.Val349Val	synonymous	Exon 10 of 15	ENSP00000542415.1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152008 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00103 AC: 257 AN: 249116 AF XY: 0.000691

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.000852

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000463 AC: 676 AN: 1459572 Hom.: 9 Cov.: 31 AF XY: 0.000401 AC XY: 291 AN XY: 725852

African (AFR) AF: 0.0165 AC: 552 AN: 33364

American (AMR) AF: 0.00102 AC: 45 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111440

Other (OTH) AF: 0.00116 AC: 70 AN: 60332

GnomAD4 genome AF: 0.00443 AC: 674 AN: 152126 Hom.: 9 Cov.: 32 AF XY: 0.00405 AC XY: 301 AN XY: 74366

African (AFR) AF: 0.0154 AC: 639 AN: 41490

American (AMR) AF: 0.00209 AC: 32 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000259 Hom.: 0

Bravo AF: 0.00515

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		-0.051
Mutation Taster		=100/0	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: rs112645348; hg19: chr8-67803127;