Variant rs3094093 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014641.3(MDC1):c.2068+23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,539,230 control chromosomes in the GnomAD database, including 679,468 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 0.96 ( 70048 hom., cov: 32)

Exomes 𝑓: 0.94 ( 609420 hom. )

Consequence

MDC1
NM_014641.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.321

Variant links:

Genes affected

MDC1 (HGNC:21163): (mediator of DNA damage checkpoint 1) The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. [provided by RefSeq, Jul 2008]

MDC1 links:

MDC1-AS1 (HGNC:):

MDC1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDC1	NM_014641.3 linkuse as main transcript	c.2068+23A>T		intron_variant		ENST00000376406.8	NP_055456.2	Q14676-1A0A1U9XBC1A1Z5I9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MDC1	ENST00000376406.8 linkuse as main transcript	c.2068+23A>T	intron_variant	5	NM_014641.3	ENSP00000365588.3	Q14676-1
MDC1	ENST00000417033.1 linkuse as main transcript	c.40+23A>T	intron_variant	2		ENSP00000408962.1	H0Y6Z8
MDC1-AS1	ENST00000442150.1 linkuse as main transcript	n.128-461T>A	intron_variant	3
MDC1	ENST00000494654.1 linkuse as main transcript	n.58+23A>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

145887

AN:

152192

Hom.:

69989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.988

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.965

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.966

GnomAD3 exomes

AF:

0.959

AC:

184311

AN:

192116

Hom.:

88528

AF XY:

0.960

AC XY:

98491

AN XY:

102564

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

0.976

Gnomad ASJ exome

AF:

0.996

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.936

Gnomad OTH exome

AF:

0.954

GnomAD4 exome

AF:

0.937

AC:

1299569

AN:

1386920

Hom.:

609420

Cov.:

AF XY:

0.939

AC XY:

640195

AN XY:

681630

show subpopulations

Gnomad4 AFR exome

AF:

0.990

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.994

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.926

Gnomad4 OTH exome

AF:

0.946

GnomAD4 genome

AF:

0.959

AC:

146005

AN:

152310

Hom.:

70048

Cov.:

AF XY:

0.959

AC XY:

71461

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.988

Gnomad4 AMR

AF:

0.965

Gnomad4 ASJ

AF:

0.993

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

0.944

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.966

Alfa

AF:

0.945

Hom.:

41706

Bravo

AF:

0.962

Asia WGS

AF:

0.997

AC:

3469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.0

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over