X-97150863-A-G

Variant names:

• chrX-97150863-A-G
• rs1886894
• NM_006729.5:c.2719+9069A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006729.5(DIAPH2):​c.2719+9069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.55 (11684 hom., 17603 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006729.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH2	NM_006729.5	MANE Select	c.2719+9069A>G		intron	N/A	NP_006720.1	O60879-1
	DIAPH2	NM_007309.4		c.2719+9069A>G		intron	N/A	NP_009293.1	O60879-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH2	ENST00000324765.13	TSL:1 MANE Select	c.2719+9069A>G		intron	N/A	ENSP00000321348.8	O60879-1
	DIAPH2	ENST00000373049.8	TSL:1	c.2719+9069A>G		intron	N/A	ENSP00000362140.4	O60879-2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 60133 AN: 110311 Hom.: 11679 Cov.: 23

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.553

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.551

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.545 AC: 60157 AN: 110358 Hom.: 11684 Cov.: 23 AF XY: 0.539 AC XY: 17603 AN XY: 32672

African (AFR) AF: 0.463 AC: 14057 AN: 30380

American (AMR) AF: 0.515 AC: 5330 AN: 10357

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 1751 AN: 2624

East Asian (EAS) AF: 0.485 AC: 1694 AN: 3496

South Asian (SAS) AF: 0.463 AC: 1213 AN: 2619

European-Finnish (FIN) AF: 0.559 AC: 3226 AN: 5772

Middle Eastern (MID) AF: 0.547 AC: 117 AN: 214

European-Non Finnish (NFE) AF: 0.599 AC: 31574 AN: 52714

Other (OTH) AF: 0.553 AC: 834 AN: 1508

Alfa AF: 0.497 Hom.: 7089

Bravo AF: 0.542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.23
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: rs1886894; hg19: chrX-96405862;