rs749569923

Variant names:

• chr2-118846940-T-A
• rs749569923
• NM_001426.4:c.228A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-118846940-T-A
• chr2-118846940-T-C
• chr2-118846940-T-G

Variant summary

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

The NM_001426.4(EN1):​c.228A>T​(p.Pro76Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. P76P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: EN1 NM_001426.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 0 publications found

Genes affected

EN1 (HGNC:3342): (engrailed homeobox 1) Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the 'engrailed' (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system. [provided by RefSeq, Jul 2008]

EN1 Gene-Disease associations (from GenCC):

• ENDOVE syndrome, limb-only type

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.314 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN1	NM_001426.4	c.228A>T	p.Pro76Pro	synonymous_variant	Exon 1 of 2	ENST00000295206.7	NP_001417.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EN1	ENST00000295206.7	c.228A>T	p.Pro76Pro	synonymous_variant	Exon 1 of 2	2	NM_001426.4	ENSP00000295206.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000921 AC: 1 AN: 108546 Hom.: 0 Cov.: 0 AF XY: 0.0000170 AC XY: 1 AN XY: 58654

African (AFR) AF: 0.00 AC: 0 AN: 1798

American (AMR) AF: 0.00 AC: 0 AN: 5046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4262

East Asian (EAS) AF: 0.00 AC: 0 AN: 2148

South Asian (SAS) AF: 0.00 AC: 0 AN: 16364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000143 AC: 1 AN: 70058

Other (OTH) AF: 0.00 AC: 0 AN: 4558

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.50
PhyloP100		0.31
Mutation Taster		=100/0	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: rs749569923; hg19: chr2-119604516;