14-69236871-G-C

Position:

• chr14-69236871-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193360.2(EXD2):​c.1292+329G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,170 control chromosomes in the GnomAD database, including 40,330 homozygotes. 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 0.72 (40330 hom., cov: 32)
• Consequence: EXD2 NM_001193360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

Genes affected

EXD2 (HGNC:20217): (exonuclease 3'-5' domain containing 2) Enables 3'-5' exonuclease activity; metal ion binding activity; and protein homodimerization activity. Involved in nucleic acid metabolic process. Located in intermediate filament cytoskeleton; mitochondrial outer membrane; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

EXD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXD2	NM_001193360.2	c.1292+329G>C		intron_variant		ENST00000685843.1	NP_001180289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXD2	ENST00000685843.1	c.1292+329G>C		intron_variant			NM_001193360.2	ENSP00000510642.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108997 AN: 152052 Hom.: 40279 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.717 AC: 109105 AN: 152170 Hom.: 40330 Cov.: 32 AF XY: 0.721 AC XY: 53670 AN XY: 74390

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.693

Alfa AF: 0.688 Hom.: 4586

Bravo AF: 0.730

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.47

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: rs4902704; hg19: chr14-69703588;