14-69209676-C-T

Variant names:

• chr14-69209676-C-T
• rs1004874222
• ENST00000413191.1:c.-260C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000413191.1(EXD2):​c.-260C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,550,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: EXD2 ENST00000413191.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12819517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000413191.1. 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
	EXD2	NM_001193360.2	MANE Select	c.206C>T	p.Ser69Leu	missense	Exon 3 of 10	NP_001180289.1	Q9NVH0-1
	EXD2	NM_001193361.2		c.206C>T	p.Ser69Leu	missense	Exon 2 of 9	NP_001180290.1	Q9NVH0-1
	EXD2	NM_001193362.2		c.206C>T	p.Ser69Leu	missense	Exon 3 of 10	NP_001180291.1	Q9NVH0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	ENST00000413191.1	TSL:1	c.-260C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000409089.1	C9JLF4
	EXD2	ENST00000685843.1	MANE Select	c.206C>T	p.Ser69Leu	missense	Exon 3 of 10	ENSP00000510642.1	Q9NVH0-1
	EXD2	ENST00000409018.7	TSL:1	c.206C>T	p.Ser69Leu	missense	Exon 2 of 9	ENSP00000387331.3	Q9NVH0-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000396 AC: 6 AN: 151528 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000148

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000872

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000858 AC: 12 AN: 1398306 Hom.: 0 Cov.: 32 AF XY: 0.00000725 AC XY: 5 AN XY: 689672

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000741 AC: 8 AN: 1078968

Other (OTH) AF: 0.0000517 AC: 3 AN: 57992

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152058 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74264

African (AFR) AF: 0.0000725 AC: 3 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.11
Sift	Benign	0.079	T
Sift4G	Benign	0.74	T
Vest4		0.15
MVP		0.53
MPC		0.13
ClinPred		0.061	T
GERP RS		4.4
Varity_R		0.058
gMVP		0.50
Mutation Taster		=94/6	polymorphism

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: rs1004874222; hg19: chr14-69676393;