X-96772151-C-T

Position:

• chrX-96772151-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.447+13893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 110,933 control chromosomes in the GnomAD database, including 1,472 homozygotes. There are 5,714 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 0.17 (1472 hom., 5714 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.447+13893C>T		intron_variant		ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.447+13893C>T		intron_variant			NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.447+13893C>T		intron_variant		1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.447+13893C>T		intron_variant		1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 18838 AN: 110880 Hom.: 1461 Cov.: 22 AF XY: 0.171 AC XY: 5685 AN XY: 33182

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0410

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0678

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.170 AC: 18891 AN: 110933 Hom.: 1472 Cov.: 22 AF XY: 0.172 AC XY: 5714 AN XY: 33245

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.182

Alfa AF: 0.148 Hom.: 1242

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.64

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: rs6620161; hg19: chrX-96027150;