X-97554499-A-G

Position:

• chrX-97554499-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH2	NM_006729.5	c.3242-44754A>G		intron_variant		ENST00000324765.13	NP_006720.1
DIAPH2-AS1	NR_125391.1	n.156+9881T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH2	ENST00000324765.13	c.3242-44754A>G		intron_variant		1	NM_006729.5	ENSP00000321348	A2
DIAPH2-AS1	ENST00000439759.6	n.126+9881T>C		intron_variant, non_coding_transcript_variant		3
DIAPH2-AS1	ENST00000579945.1	n.154+9881T>C		intron_variant, non_coding_transcript_variant		1
DIAPH2-AS1	ENST00000445414.1	n.350-21070T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 51866 AN: 110690 Hom.: 8681 Cov.: 22 AF XY: 0.462 AC XY: 15227 AN XY: 32940

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

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.462

Alfa AF: 0.507 Hom.: 50065

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs897918; hg19: chrX-96809498;