X-96758171-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_006729.5(DIAPH2):c.360C>T(p.Asn120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000449 in 1,202,032 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.000045 (0 hom. 11 hem.)
• Consequence: DIAPH2 NM_006729.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.374

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant X-96758171-C-T is Benign according to our data. Variant chrX-96758171-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.374 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIAPH2	NM_006729.5	c.360C>T	p.Asn120=	synonymous_variant	4/27	ENST00000324765.13
DIAPH2	NM_007309.4	c.360C>T	p.Asn120=	synonymous_variant	4/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIAPH2	ENST00000324765.13	c.360C>T	p.Asn120=	synonymous_variant	4/27	1	NM_006729.5	A2
DIAPH2	ENST00000373049.8	c.360C>T	p.Asn120=	synonymous_variant	4/27	1		P3

Frequencies

GnomAD3 genomes AF: 0.0000449 AC: 5 AN: 111370 Hom.: 0 Cov.: 22 AF XY: 0.0000893 AC XY: 3 AN XY: 33604

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000957

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000378

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000980 AC: 17 AN: 173417 Hom.: 0 AF XY: 0.000102 AC XY: 6 AN XY: 58901

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000280

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000384

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000634

Gnomad NFE exome AF: 0.0000507

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000449 AC: 49 AN: 1090608 Hom.: 0 Cov.: 29 AF XY: 0.0000308 AC XY: 11 AN XY: 357282

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000495

Gnomad4 NFE exome AF: 0.0000393

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111424 Hom.: 0 Cov.: 22 AF XY: 0.0000891 AC XY: 3 AN XY: 33668

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000956

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000168

Gnomad4 NFE AF: 0.0000378

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000162 Hom.: 1

Bravo AF: 0.0000604

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

DIAPH2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	3.6
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200157443; hg19: chrX-96013170; COSMIC: COSV61282766;