rs397507559

Variant names:

• chr9-35075706-AAAACACCTCA-G
• rs397507559
• NM_004629.2:c.1182_1192delTGAGGTGTTTTinsC

Your query was ambiguous. Multiple possible variants found:

• chr9-35075705-AAAAACACCTCA-AG
• chr9-35075705-AAAAACACCTCA-AA

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_004629.2(FANCG):​c.1182_1192delTGAGGTGTTTTinsC​(p.Glu395TrpfsTer5) variant causes a frameshift, synonymous change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P394P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: FANCG NM_004629.2 frameshift, synonymous
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 6.64
• Publications: 6 publications found

Genes affected

FANCG (HGNC:3588): (FA complementation group G) 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 G. [provided by RefSeq, Jul 2008]

FANCG Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group G

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-35075706-AAAACACCTCA-G is Pathogenic according to our data. Variant chr9-35075706-AAAACACCTCA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 969518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004629.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCG	NM_004629.2	MANE Select	c.1182_1192delTGAGGTGTTTTinsC	p.Glu395TrpfsTer5	frameshift synonymous	Exon 10 of 14	NP_004620.1	O15287

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCG	ENST00000378643.8	TSL:1 MANE Select	c.1182_1192delTGAGGTGTTTTinsC	p.Glu395TrpfsTer5	frameshift synonymous	Exon 10 of 14	ENSP00000367910.4	O15287
	FANCG	ENST00000425676.5	TSL:1	n.*658_*668delTGAGGTGTTTTinsC		non_coding_transcript_exon	Exon 9 of 13	ENSP00000412793.1	F8WC08
	FANCG	ENST00000425676.5	TSL:1	n.*658_*668delTGAGGTGTTTTinsC		3_prime_UTR	Exon 9 of 13	ENSP00000412793.1	F8WC08

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Fanconi anemia complementation group G (2)
1	-	-	Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs397507559; hg19: chr9-35075703;