rs2302162

chr16-89778879-A-Gchr16-89778879-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000135.4(FANCA):c.1777-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,613,612 control chromosomes in the GnomAD database, including 5,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (424 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5398 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.329

Genes affected

FANCA (HGNC:3582): (FA complementation group A) 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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89778879-A-G is Benign according to our data. Variant chr16-89778879-A-G is described in ClinVar as [Benign]. Clinvar id is 255239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.1777-29T>C		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.1777-29T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.1777-29T>C		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9114 AN: 151862 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0546

GnomAD3 exomes AF: 0.0674 AC: 16959 AN: 251460 Hom.: 1028 AF XY: 0.0665 AC XY: 9042 AN XY: 135902

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.0197

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.0211

Gnomad FIN exome AF: 0.0585

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.0577

GnomAD4 exome AF: 0.0792 AC: 115813 AN: 1461632 Hom.: 5398 Cov.: 34 AF XY: 0.0777 AC XY: 56486 AN XY: 727132

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.0570

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.0222

Gnomad4 FIN exome AF: 0.0573

Gnomad4 NFE exome AF: 0.0867

Gnomad4 OTH exome AF: 0.0829

GnomAD4 genome AF: 0.0600 AC: 9120 AN: 151980 Hom.: 424 Cov.: 32 AF XY: 0.0580 AC XY: 4312 AN XY: 74306

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.0271

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0834

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0458 Hom.: 44

Bravo AF: 0.0577

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fanconi anemia complementation group A Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.17
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2302162; hg19: chr16-89845287; COSMIC: COSV66880567; COSMIC: COSV66880567;