X-97062194-C-G

Position:

• chrX-97062194-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000324765.13(DIAPH2):​c.2051-10747C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 111,138 control chromosomes in the GnomAD database, including 1,051 homozygotes. There are 4,664 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 0.14 (1051 hom., 4664 hem., cov: 23)
• Consequence: DIAPH2 ENST00000324765.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.2051-10747C>G		intron_variant		ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.2051-10747C>G		intron_variant			NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.2051-10747C>G		intron_variant		1	NM_006729.5	ENSP00000321348	A2
DIAPH2	ENST00000373049.8	c.2051-10747C>G		intron_variant		1		ENSP00000362140	P3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15953 AN: 111085 Hom.: 1045 Cov.: 23 AF XY: 0.140 AC XY: 4658 AN XY: 33321

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.144 AC: 15971 AN: 111138 Hom.: 1051 Cov.: 23 AF XY: 0.140 AC XY: 4664 AN XY: 33384

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.171

Alfa AF: 0.0650 Hom.: 329

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.54

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: rs10521495; hg19: chrX-96317193;