rs233214

Variant names:

• chrX-96887520-C-T
• rs233214
• NM_006729.5:c.587+5802C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006729.5(DIAPH2):​c.587+5802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 109,628 control chromosomes in the GnomAD database, including 10,693 homozygotes. There are 15,252 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 0.49 (10693 hom., 15252 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 2 publications found

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]

DIAPH2 Gene-Disease associations (from GenCC):

• premature ovarian failure 2A

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.587+5802C>T		intron_variant	Intron 5 of 26	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.587+5802C>T		intron_variant	Intron 5 of 26		NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.587+5802C>T		intron_variant	Intron 5 of 26	1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.587+5802C>T		intron_variant	Intron 5 of 26	1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 53329 AN: 109580 Hom.: 10701 Cov.: 22

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.487 AC: 53354 AN: 109628 Hom.: 10693 Cov.: 22 AF XY: 0.477 AC XY: 15252 AN XY: 31970

African (AFR) AF: 0.774 AC: 23291 AN: 30103

American (AMR) AF: 0.477 AC: 4879 AN: 10228

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 904 AN: 2624

East Asian (EAS) AF: 0.367 AC: 1271 AN: 3465

South Asian (SAS) AF: 0.273 AC: 689 AN: 2526

European-Finnish (FIN) AF: 0.313 AC: 1785 AN: 5700

Middle Eastern (MID) AF: 0.502 AC: 105 AN: 209

European-Non Finnish (NFE) AF: 0.370 AC: 19467 AN: 52607

Other (OTH) AF: 0.466 AC: 700 AN: 1502

Alfa AF: 0.410 Hom.: 48910

Bravo AF: 0.514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.55
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs233214; hg19: chrX-96142519;