X-97423193-C-G

Variant names:

• chrX-97423193-C-G
• rs2353564
• NM_006729.5:c.3146-6457C>G

Variant summary

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

The NM_006729.5(DIAPH2):​c.3146-6457C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 109,696 control chromosomes in the GnomAD database, including 6,949 homozygotes. There are 13,172 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 0.42 (6949 hom., 13172 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

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.3146-6457C>G		intron	N/A	NP_006720.1	O60879-1
	DIAPH2	NM_007309.4		c.3146-6457C>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.3146-6457C>G		intron	N/A	ENSP00000321348.8	O60879-1
	DIAPH2	ENST00000373049.8	TSL:1	c.3146-6457C>G		intron	N/A	ENSP00000362140.4	O60879-2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 45988 AN: 109645 Hom.: 6958 Cov.: 22

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.419 AC: 45998 AN: 109696 Hom.: 6949 Cov.: 22 AF XY: 0.411 AC XY: 13172 AN XY: 32040

African (AFR) AF: 0.439 AC: 13225 AN: 30134

American (AMR) AF: 0.424 AC: 4336 AN: 10227

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1296 AN: 2612

East Asian (EAS) AF: 0.571 AC: 1954 AN: 3421

South Asian (SAS) AF: 0.504 AC: 1260 AN: 2501

European-Finnish (FIN) AF: 0.372 AC: 2145 AN: 5763

Middle Eastern (MID) AF: 0.502 AC: 106 AN: 211

European-Non Finnish (NFE) AF: 0.395 AC: 20790 AN: 52672

Other (OTH) AF: 0.438 AC: 651 AN: 1488

Alfa AF: 0.391 Hom.: 2513

Bravo AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.34
PhyloP100		0.67
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: rs2353564; hg19: chrX-96678192;