rs10521496

Variant names:

• chrX-97043550-G-A
• rs10521496
• NM_006729.5:c.2051-29391G>A

Variant summary

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

The NM_006729.5(DIAPH2):​c.2051-29391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 109,294 control chromosomes in the GnomAD database, including 6,946 homozygotes. There are 12,688 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 0.41 (6946 hom., 12688 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.2051-29391G>A		intron_variant	Intron 17 of 26	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.2051-29391G>A		intron_variant	Intron 17 of 26		NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.2051-29391G>A		intron_variant	Intron 17 of 26	1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.2051-29391G>A		intron_variant	Intron 17 of 26	1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 44598 AN: 109242 Hom.: 6945 Cov.: 22

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.483

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.408 AC: 44612 AN: 109294 Hom.: 6946 Cov.: 22 AF XY: 0.400 AC XY: 12688 AN XY: 31756

African (AFR) AF: 0.287 AC: 8682 AN: 30209

American (AMR) AF: 0.321 AC: 3306 AN: 10300

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1394 AN: 2619

East Asian (EAS) AF: 0.302 AC: 1046 AN: 3460

South Asian (SAS) AF: 0.536 AC: 1360 AN: 2537

European-Finnish (FIN) AF: 0.510 AC: 2844 AN: 5577

Middle Eastern (MID) AF: 0.488 AC: 104 AN: 213

European-Non Finnish (NFE) AF: 0.475 AC: 24824 AN: 52226

Other (OTH) AF: 0.421 AC: 626 AN: 1486

Alfa AF: 0.416 Hom.: 7036

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-0.36
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: rs10521496; hg19: chrX-96298549;