X-97151055-C-T

Variant names:

• chrX-97151055-C-T
• rs1012930
• NM_006729.5:c.2719+9261C>T

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+9261C>T 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 (11789 hom., 17725 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• 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=-0.96).

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+9261C>T		intron	N/A	NP_006720.1	O60879-1
	DIAPH2	NM_007309.4		c.2719+9261C>T		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+9261C>T		intron	N/A	ENSP00000321348.8	O60879-1
	DIAPH2	ENST00000373049.8	TSL:1	c.2719+9261C>T		intron	N/A	ENSP00000362140.4	O60879-2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 60480 AN: 110096 Hom.: 11784 Cov.: 22

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.549

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.554

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: 0.549 AC: 60500 AN: 110148 Hom.: 11789 Cov.: 22 AF XY: 0.546 AC XY: 17725 AN XY: 32472

African (AFR) AF: 0.475 AC: 14391 AN: 30306

American (AMR) AF: 0.515 AC: 5323 AN: 10326

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 1732 AN: 2622

East Asian (EAS) AF: 0.490 AC: 1706 AN: 3480

South Asian (SAS) AF: 0.463 AC: 1203 AN: 2598

European-Finnish (FIN) AF: 0.566 AC: 3239 AN: 5720

Middle Eastern (MID) AF: 0.542 AC: 117 AN: 216

European-Non Finnish (NFE) AF: 0.599 AC: 31591 AN: 52696

Other (OTH) AF: 0.556 AC: 839 AN: 1508

Alfa AF: 0.569 Hom.: 4248

Bravo AF: 0.545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		0.30
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1012930;

hg19: chrX-96406054;