rs9879080

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018115.3(FANCD2):​c.784-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,587,748 control chromosomes in the GnomAD database, including 27,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5011 hom., cov: 32)
Exomes 𝑓: 0.17 ( 22220 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.872
Variant links:
Genes affected
FANCD2 (HGNC:3585): (FA complementation group D2) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 AND BRCA2) involved in homology-directed DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 3-10042540-C-T is Benign according to our data. Variant chr3-10042540-C-T is described in ClinVar as [Benign]. Clinvar id is 257087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-10042540-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FANCD2NM_001018115.3 linkuse as main transcriptc.784-19C>T intron_variant ENST00000675286.1 NP_001018125.1 Q9BXW9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FANCD2ENST00000675286.1 linkuse as main transcriptc.784-19C>T intron_variant NM_001018115.3 ENSP00000502379.1 Q9BXW9-2

Frequencies

GnomAD3 genomes
AF:
0.226
AC:
34299
AN:
151946
Hom.:
5005
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.419
Gnomad AMI
AF:
0.269
Gnomad AMR
AF:
0.156
Gnomad ASJ
AF:
0.150
Gnomad EAS
AF:
0.0655
Gnomad SAS
AF:
0.161
Gnomad FIN
AF:
0.117
Gnomad MID
AF:
0.143
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.194
GnomAD3 exomes
AF:
0.168
AC:
42343
AN:
251358
Hom.:
4336
AF XY:
0.166
AC XY:
22494
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.432
Gnomad AMR exome
AF:
0.158
Gnomad ASJ exome
AF:
0.159
Gnomad EAS exome
AF:
0.0654
Gnomad SAS exome
AF:
0.175
Gnomad FIN exome
AF:
0.120
Gnomad NFE exome
AF:
0.159
Gnomad OTH exome
AF:
0.160
GnomAD4 exome
AF:
0.169
AC:
242439
AN:
1435684
Hom.:
22220
Cov.:
27
AF XY:
0.168
AC XY:
120441
AN XY:
715928
show subpopulations
Gnomad4 AFR exome
AF:
0.430
Gnomad4 AMR exome
AF:
0.162
Gnomad4 ASJ exome
AF:
0.157
Gnomad4 EAS exome
AF:
0.0567
Gnomad4 SAS exome
AF:
0.178
Gnomad4 FIN exome
AF:
0.124
Gnomad4 NFE exome
AF:
0.167
Gnomad4 OTH exome
AF:
0.174
GnomAD4 genome
AF:
0.226
AC:
34335
AN:
152064
Hom.:
5011
Cov.:
32
AF XY:
0.220
AC XY:
16341
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.419
Gnomad4 AMR
AF:
0.155
Gnomad4 ASJ
AF:
0.150
Gnomad4 EAS
AF:
0.0655
Gnomad4 SAS
AF:
0.161
Gnomad4 FIN
AF:
0.117
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.194
Alfa
AF:
0.190
Hom.:
597
Bravo
AF:
0.240
Asia WGS
AF:
0.124
AC:
435
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2 Benign:2
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 11, 2019- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Fanconi anemia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitterclinical testingNational Health Laboratory Service, Universitas Academic Hospital and University of the Free StateApr 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
7.4
DANN
Benign
0.50

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

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

Other links and lift over

dbSNP: rs9879080; hg19: chr3-10084224; COSMIC: COSV55047416; COSMIC: COSV55047416; API