Genetic Variant AFF2:c.-422_-414dupCGCCGCCGC (chrX-148500637-T-TGCCGCCGCC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002025.4(AFF2):c.-422_-414dupCGCCGCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 879 hom., 1429 hem., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

AFF2
NM_002025.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80

Variant links:

Genes affected

AFF2 (HGNC:3776): (ALF transcription elongation factor 2) This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]

AFF2 links:

ENSG00000237741 (HGNC:):

ENSG00000237741 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF2	NM_002025.4 link	c.-422_-414dupCGCCGCCGC		5_prime_UTR_variant	Exon 1 of 21	ENST00000370460.7	NP_002016.2	P51816-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AFF2	ENST00000370460 link	c.-422_-414dupCGCCGCCGC	5_prime_UTR_variant	Exon 1 of 21	5	NM_002025.4	ENSP00000359489.2	P51816-1
AFF2	ENST00000342251.7 link	c.-461_-460insGCCGCCGCC	upstream_gene_variant		1		ENSP00000345459.4	P51816-3
ENSG00000237741	ENST00000456981.1 link	n.-31_-23dupGGCGGCGGC	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

9105

AN:

73058

Hom.:

881

Cov.:

AF XY:

0.0926

AC XY:

1428

AN XY:

15420

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.0773

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.159

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

613

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

163

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.125

AC:

9100

AN:

73043

Hom.:

879

Cov.:

AF XY:

0.0926

AC XY:

1429

AN XY:

15431

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.0773

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over