chrX-96879433-C-T

Variant names:

• chrX-96879433-C-T
• rs707289
• NM_006729.5:c.448-2146C>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.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
• Publications: 0 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=-0.96).
• 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 rank	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.448-2146C>T		intron_variant	Intron 4 of 26	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.448-2146C>T		intron_variant	Intron 4 of 26		NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.448-2146C>T		intron_variant	Intron 4 of 26	1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.448-2146C>T		intron_variant	Intron 4 of 26	1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 57027 AN: 110264 Hom.: 12205 Cov.: 23

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

African (AFR) AF: 0.175 AC: 5331 AN: 30429

American (AMR) AF: 0.538 AC: 5563 AN: 10337

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 1994 AN: 2634

East Asian (EAS) AF: 0.620 AC: 2155 AN: 3475

South Asian (SAS) AF: 0.739 AC: 1881 AN: 2545

European-Finnish (FIN) AF: 0.691 AC: 3989 AN: 5774

Middle Eastern (MID) AF: 0.591 AC: 127 AN: 215

European-Non Finnish (NFE) AF: 0.657 AC: 34632 AN: 52732

Other (OTH) AF: 0.553 AC: 826 AN: 1495

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
PhyloP100		0.18
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: rs707289; hg19: chrX-96134432;