chr22-38566727-C-T

Position:

• chr22-38566727-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_007068.4(DMC1):​c.106G>A​(p.Asp36Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DMC1 NM_007068.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.52

Genes affected

DMC1 (HGNC:2927): (DNA meiotic recombinase 1) This gene encodes a member of the superfamily of recombinases (also called DNA strand-exchange proteins). Recombinases are important for repairing double-strand DNA breaks during mitosis and meiosis. This protein, which is evolutionarily conserved, is reported to be essential for meiotic homologous recombination and may thus play an important role in generating diversity of genetic information. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

DMC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMC1	NM_007068.4	c.106G>A	p.Asp36Asn	missense_variant	4/14	ENST00000216024.7	NP_008999.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMC1	ENST00000216024.7	c.106G>A	p.Asp36Asn	missense_variant	4/14	1	NM_007068.4	ENSP00000216024.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461624 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.78	.;D;.;T;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Pathogenic	3.6	H;H;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-4.0	D;D;D;.;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;.;D;.
Polyphen		0.99, 1.0	.;D;.;D;.
Vest4		0.82
MutPred		0.67		Gain of MoRF binding (P = 0.0338);Gain of MoRF binding (P = 0.0338);Gain of MoRF binding (P = 0.0338);Gain of MoRF binding (P = 0.0338);Gain of MoRF binding (P = 0.0338);
MVP		0.82
MPC		1.0
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.76
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1569172827; hg19: chr22-38962732;