Genetic Variant NM_002025.4:c.-449_-414dupCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC (chrX-148500637-T-TGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_002025.4(AFF2):c.-449_-414dupCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC 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 0.0028 ( 12 hom., 16 hem., cov: 0)

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.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00284 (208/73128) while in subpopulation NFE AF= 0.00342 (130/38022). AF 95% confidence interval is 0.00294. There are 12 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFF2	NM_002025.4 link	c.-449_-414dupCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC		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.-449_-414dupCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC	5_prime_UTR_variant	Exon 1 of 21	5	NM_002025.4	ENSP00000359489.2	P51816-1
AFF2	ENST00000342251.7 link	c.-461_-460insGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCC	upstream_gene_variant		1		ENSP00000345459.4	P51816-3
ENSG00000237741	ENST00000456981.1 link	n.-58_-23dupGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

208

AN:

73143

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

15463

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00300

Gnomad EAS

AF:

0.00200

Gnomad SAS

AF:

0.00144

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.00423

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00284

AC:

208

AN:

73128

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

15474

show subpopulations

Gnomad4 AFR

AF:

0.00254

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00300

Gnomad4 EAS

AF:

0.00201

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00342

Gnomad4 OTH

AF:

0.00420

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