14-69236871-G-C

Variant names:

• chr14-69236871-G-C
• rs4902704
• NM_001193360.2:c.1292+329G>C

Variant summary

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

The ENST00000685843.1(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 ENST00000685843.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 6 publications found

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]

GALNT16-AS1 (HGNC:55435): (GALNT16 and EXD2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685843.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	NM_001193360.2	MANE Select	c.1292+329G>C		intron	N/A	NP_001180289.1
	EXD2	NM_001193361.2		c.1292+329G>C		intron	N/A	NP_001180290.1
	EXD2	NM_001193362.2		c.1292+329G>C		intron	N/A	NP_001180291.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	ENST00000685843.1	MANE Select	c.1292+329G>C		intron	N/A	ENSP00000510642.1
	EXD2	ENST00000409018.7	TSL:1	c.1292+329G>C		intron	N/A	ENSP00000387331.3
	EXD2	ENST00000409675.5	TSL:1	c.917+329G>C		intron	N/A	ENSP00000386762.1

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

African (AFR) AF: 0.872 AC: 36225 AN: 41528

American (AMR) AF: 0.741 AC: 11324 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4875 AN: 5184

South Asian (SAS) AF: 0.827 AC: 3991 AN: 4828

European-Finnish (FIN) AF: 0.617 AC: 6525 AN: 10572

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42051 AN: 67990

Other (OTH) AF: 0.693 AC: 1463 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.47
PhyloP100		-1.7
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: rs4902704; hg19: chr14-69703588;