14-69209562-G-A

Variant names:

• chr14-69209562-G-A
• rs182466488
• NM_001193360.2:c.92G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001193360.2(EXD2):​c.92G>A​(p.Arg31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,550,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: EXD2 NM_001193360.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057209134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193360.2. 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.92G>A	p.Arg31His	missense	Exon 3 of 10	NP_001180289.1	Q9NVH0-1
	EXD2	NM_001193361.2		c.92G>A	p.Arg31His	missense	Exon 2 of 9	NP_001180290.1	Q9NVH0-1
	EXD2	NM_001193362.2		c.92G>A	p.Arg31His	missense	Exon 3 of 10	NP_001180291.1	Q9NVH0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD2	ENST00000685843.1	MANE Select	c.92G>A	p.Arg31His	missense	Exon 3 of 10	ENSP00000510642.1	Q9NVH0-1
	EXD2	ENST00000409018.7	TSL:1	c.92G>A	p.Arg31His	missense	Exon 2 of 9	ENSP00000387331.3	Q9NVH0-1
	EXD2	ENST00000413191.1	TSL:1	c.-374G>A		5_prime_UTR	Exon 3 of 6	ENSP00000409089.1	C9JLF4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

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: 0.0000735

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000200 AC: 30 AN: 150252 AF XY: 0.000186

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.000651

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 141 AN: 1398334 Hom.: 0 Cov.: 31 AF XY: 0.0000870 AC XY: 60 AN XY: 689684

African (AFR) AF: 0.0000633 AC: 2 AN: 31598

American (AMR) AF: 0.000924 AC: 33 AN: 35702

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.000151 AC: 12 AN: 79234

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: 0.0000779 AC: 84 AN: 1078980

Other (OTH) AF: 0.000172 AC: 10 AN: 58010

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74420

African (AFR) AF: 0.0000241 AC: 1 AN: 41526

American (AMR) AF: 0.00144 AC: 22 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.000194 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.36
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.11
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Vest4		0.14
MVP		0.45
MPC		0.19
ClinPred		0.050	T
GERP RS		3.5
Varity_R		0.019
gMVP		0.38
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs182466488; hg19: chr14-69676279;