NM_006729.5:c.3242-44754A>G

Variant names:

• chrX-97554499-A-G
• rs897918
• NM_006729.5:c.3242-44754A>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.3242-44754A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 110,741 control chromosomes in the GnomAD database, including 8,686 homozygotes. There are 15,269 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 0.47 (8686 hom., 15269 hem., cov: 22)
• Consequence: DIAPH2 NM_006729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 3 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-AS1 (HGNC:16972): (DIAPH2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006729.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH2	NM_006729.5	MANE Select	c.3242-44754A>G		intron	N/A	NP_006720.1	O60879-1
	DIAPH2-AS1	NR_125391.1		n.156+9881T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH2	ENST00000324765.13	TSL:1 MANE Select	c.3242-44754A>G		intron	N/A	ENSP00000321348.8	O60879-1
	DIAPH2-AS1	ENST00000579945.1	TSL:1	n.154+9881T>C		intron	N/A
	DIAPH2-AS1	ENST00000439759.6	TSL:3	n.126+9881T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.469 AC: 51866 AN: 110690 Hom.: 8681 Cov.: 22

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.469 AC: 51911 AN: 110741 Hom.: 8686 Cov.: 22 AF XY: 0.463 AC XY: 15269 AN XY: 33001

African (AFR) AF: 0.400 AC: 12211 AN: 30520

American (AMR) AF: 0.472 AC: 4902 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1120 AN: 2637

East Asian (EAS) AF: 0.452 AC: 1578 AN: 3490

South Asian (SAS) AF: 0.422 AC: 1111 AN: 2634

European-Finnish (FIN) AF: 0.460 AC: 2697 AN: 5868

Middle Eastern (MID) AF: 0.448 AC: 95 AN: 212

European-Non Finnish (NFE) AF: 0.513 AC: 27108 AN: 52833

Other (OTH) AF: 0.462 AC: 691 AN: 1495

Alfa AF: 0.499 Hom.: 65136

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.80
PhyloP100		0.42
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: rs897918; hg19: chrX-96809498;