14-74239609-A-C

Variant names:

• chr14-74239609-A-C
• rs894661629
• NM_182894.3:c.48A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_182894.3(VSX2):​c.48A>C​(p.Thr16Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T16T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: VSX2 NM_182894.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 0 publications found

Genes affected

VSX2 (HGNC:1975): (visual system homeobox 2) This gene encodes a homeobox protein originally described as a retina-specific transcription factor. Mutations in this gene are associated with microphthalmia, cataracts and iris abnormalities. [provided by RefSeq, Oct 2009]

VSX2 Gene-Disease associations (from GenCC):

• isolated microphthalmia 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• microphthalmia, isolated, with coloboma 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• microphthalmia

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• isolated anophthalmia-microphthalmia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.226 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182894.3. 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
	VSX2	NM_182894.3	MANE Select	c.48A>C	p.Thr16Thr	synonymous	Exon 1 of 5	NP_878314.1	P58304

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSX2	ENST00000261980.3	TSL:1 MANE Select	c.48A>C	p.Thr16Thr	synonymous	Exon 1 of 5	ENSP00000261980.2	P58304

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000647 AC: 1 AN: 154678 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399034 Hom.: 0 Cov.: 32 AF XY: 0.00000435 AC XY: 3 AN XY: 690016

African (AFR) AF: 0.00 AC: 0 AN: 31598

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078966

Other (OTH) AF: 0.00 AC: 0 AN: 57996

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.3
DANN	Benign	0.59
PhyloP100		0.23
PromoterAI		0.0059	Neutral

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: rs894661629; hg19: chr14-74706312;