Genetic Variant NM_002025.4:c.-416_-414dupCGC (chrX-148500637-T-TGCC) – 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.-416_-414dupCGC 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 0.13 ( 678 hom., 1506 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF2	NM_002025.4 link	c.-416_-414dupCGC		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.-416_-414dupCGC	5_prime_UTR_variant	Exon 1 of 21	5	NM_002025.4	ENSP00000359489.2	P51816-1
AFF2	ENST00000342251.7 link	c.-461_-460insGCC	upstream_gene_variant		1		ENSP00000345459.4	P51816-3
ENSG00000237741	ENST00000456981.1 link	n.-25_-23dupGGC	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

9217

AN:

73091

Hom.:

676

Cov.:

AF XY:

0.0976

AC XY:

1507

AN XY:

15445

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.0788

Gnomad AMR

AF:

0.0958

Gnomad ASJ

AF:

0.0925

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.0712

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.109

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:

0.126

AC:

9218

AN:

73076

Hom.:

678

Cov.:

AF XY:

0.0974

AC XY:

1506

AN XY:

15456

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0958

Gnomad4 ASJ

AF:

0.0925

Gnomad4 EAS

AF:

0.0622

Gnomad4 SAS

AF:

0.0699

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.115

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