16-89799595-ATTAAC-A

Position:

• chr16-89799595-ATTAAC-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The ENST00000389301.8(FANCA):​c.826+5_826+9del variant causes a splice donor 5th base, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FANCA ENST00000389301.8 splice_donor_5th_base, intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.51

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-89799595-ATTAAC-A is Pathogenic according to our data. Variant chr16-89799595-ATTAAC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 210973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4	c.826+5_826+9del		splice_donor_5th_base_variant, intron_variant		ENST00000389301.8	NP_000126.2
FANCA	NM_001018112.3	c.826+5_826+9del		splice_donor_5th_base_variant, intron_variant			NP_001018122.1
FANCA	NM_001286167.3	c.826+5_826+9del		splice_donor_5th_base_variant, intron_variant			NP_001273096.1
FANCA	NM_001351830.2	c.730+5_730+9del		splice_donor_5th_base_variant, intron_variant			NP_001338759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8	c.826+5_826+9del		splice_donor_5th_base_variant, intron_variant		1	NM_000135.4	ENSP00000373952	P1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia complementation group A Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 26, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs797045570; hg19: chr16-89866003;