rs6620161

Variant names:

• chrX-96772151-C-T
• rs6620161
• NM_006729.5:c.447+13893C>T

Variant summary

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

The NM_006729.5(DIAPH2):​c.447+13893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 110,933 control chromosomes in the GnomAD database, including 1,472 homozygotes. There are 5,714 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 0.17 (1472 hom., 5714 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.447+13893C>T		intron_variant	Intron 4 of 26	ENST00000324765.13	NP_006720.1
DIAPH2	NM_007309.4	c.447+13893C>T		intron_variant	Intron 4 of 26		NP_009293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.447+13893C>T		intron_variant	Intron 4 of 26	1	NM_006729.5	ENSP00000321348.8
DIAPH2	ENST00000373049.8	c.447+13893C>T		intron_variant	Intron 4 of 26	1		ENSP00000362140.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 18838 AN: 110880 Hom.: 1461 Cov.: 22

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0410

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0678

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.170 AC: 18891 AN: 110933 Hom.: 1472 Cov.: 22 AF XY: 0.172 AC XY: 5714 AN XY: 33245

African (AFR) AF: 0.234 AC: 7145 AN: 30530

American (AMR) AF: 0.354 AC: 3675 AN: 10375

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 288 AN: 2632

East Asian (EAS) AF: 0.327 AC: 1153 AN: 3527

South Asian (SAS) AF: 0.173 AC: 460 AN: 2665

European-Finnish (FIN) AF: 0.118 AC: 695 AN: 5866

Middle Eastern (MID) AF: 0.0648 AC: 14 AN: 216

European-Non Finnish (NFE) AF: 0.0975 AC: 5161 AN: 52942

Other (OTH) AF: 0.182 AC: 272 AN: 1497

Alfa AF: 0.148 Hom.: 1242

Bravo AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.64
PhyloP100		-0.034
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: rs6620161; hg19: chrX-96027150;