X-97423193-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIAPH2	NM_006729.5	c.3146-6457C>G		intron_variant		ENST00000324765.13
DIAPH2	NM_007309.4	c.3146-6457C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIAPH2	ENST00000324765.13	c.3146-6457C>G		intron_variant		1	NM_006729.5	A2
DIAPH2	ENST00000373049.8	c.3146-6457C>G		intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 45988 AN: 109645 Hom.: 6958 Cov.: 22 AF XY: 0.411 AC XY: 13148 AN XY: 31979

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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.438

Alfa AF: 0.391 Hom.: 2513

Bravo AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.0
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2353564; hg19: chrX-96678192;