6-35452759-C-G

Variant names:

• chr6-35452759-C-G
• rs890865684
• NM_021922.3:c.214C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021922.3(FANCE):​c.214C>G​(p.Pro72Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FANCE NM_021922.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

Genes affected

FANCE (HGNC:3586): (FA complementation group E) 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 E. [provided by RefSeq, Jul 2008]

FANCE Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group E

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	NM_021922.3	MANE Select	c.214C>G	p.Pro72Ala	missense	Exon 1 of 10	NP_068741.1
	FANCE	NM_001410876.1		c.214C>G	p.Pro72Ala	missense	Exon 1 of 8	NP_001397805.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.214C>G	p.Pro72Ala	missense	Exon 1 of 10	ENSP00000229769.2
	FANCE	ENST00000696264.1		c.214C>G	p.Pro72Ala	missense	Exon 1 of 8	ENSP00000512511.1
	FANCE	ENST00000648059.1		n.214C>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000497902.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Benign	0.51	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.62		Loss of loop (P = 0.0022)
MVP		0.80
MPC		0.52
ClinPred		0.96	D
GERP RS		5.2
PromoterAI		0.0032	Neutral
Varity_R		0.13
gMVP		0.34
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs890865684; hg19: chr6-35420536;