22-38551830-C-T

Position:

• chr22-38551830-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007068.4(DMC1):​c.421+836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 149,770 control chromosomes in the GnomAD database, including 5,066 homozygotes. 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: 𝑓 0.24 (5066 hom., cov: 28)
• Consequence: DMC1 NM_007068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMC1	NM_007068.4	c.421+836G>A		intron_variant		ENST00000216024.7	NP_008999.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMC1	ENST00000216024.7	c.421+836G>A		intron_variant		1	NM_007068.4	ENSP00000216024.2
DMC1	ENST00000428462.6	c.421+836G>A		intron_variant		2		ENSP00000412703.2
DMC1	ENST00000439567.5	c.421+836G>A		intron_variant		3		ENSP00000391385.1
DMC1	ENST00000478820.1	n.596+836G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36478 AN: 149684 Hom.: 5064 Cov.: 28

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 36488 AN: 149770 Hom.: 5066 Cov.: 28 AF XY: 0.245 AC XY: 17822 AN XY: 72820

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.257

Alfa AF: 0.190 Hom.: 612

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs5757133; hg19: chr22-38947835; COSMIC: COSV53258795; COSMIC: COSV53258795;