rs707289

Positions:

• chrX-96879433-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006729.5(DIAPH2):​c.448-2146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 110,313 control chromosomes in the GnomAD database, including 12,202 homozygotes. There are 16,912 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (12202 hom., 16912 hem., cov: 23)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

Genes affected

DIAPH2 (HGNC:2877): (diaphanous related formin 2) The product of this gene belongs to the diaphanous subfamily of the formin homology family of proteins. This gene may play a role in the development and normal function of the ovaries. Defects in this gene have been linked to premature ovarian failure 2. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.448-2146C>T		intron_variant		ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.448-2146C>T		intron_variant			NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.448-2146C>T		intron_variant		1	NM_006729.5	ENSP00000321348	A2
DIAPH2	ENST00000373049.8	c.448-2146C>T		intron_variant		1		ENSP00000362140	P3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 57027 AN: 110264 Hom.: 12205 Cov.: 23 AF XY: 0.519 AC XY: 16896 AN XY: 32552

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.517 AC: 57040 AN: 110313 Hom.: 12202 Cov.: 23 AF XY: 0.519 AC XY: 16912 AN XY: 32611

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.553

Alfa AF: 0.548 Hom.: 5642

Bravo AF: 0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs707289; hg19: chrX-96134432;