NM_006729.5:c.2051-10747C>G

Variant names:

• chrX-97062194-C-G
• rs10521495
• NM_006729.5:c.2051-10747C>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.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 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 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=-0.93).
• 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 rank	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.2051-10747C>G		intron_variant	Intron 17 of 26	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.2051-10747C>G		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.2051-10747C>G		intron_variant	Intron 17 of 26	1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.2051-10747C>G		intron_variant	Intron 17 of 26	1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15953 AN: 111085 Hom.: 1045 Cov.: 23

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

African (AFR) AF: 0.0403 AC: 1238 AN: 30696

American (AMR) AF: 0.236 AC: 2464 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 490 AN: 2634

East Asian (EAS) AF: 0.335 AC: 1169 AN: 3487

South Asian (SAS) AF: 0.176 AC: 462 AN: 2620

European-Finnish (FIN) AF: 0.126 AC: 745 AN: 5895

Middle Eastern (MID) AF: 0.107 AC: 23 AN: 214

European-Non Finnish (NFE) AF: 0.169 AC: 8957 AN: 52955

Other (OTH) AF: 0.171 AC: 259 AN: 1519

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
PhyloP100		-1.1
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: rs10521495; hg19: chrX-96317193;