chr14-100728998-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_003836.7(DLK1):c.194A>G(p.His65Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000902 in 1,613,860 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 Benign (★).
Frequency
Consequence
NM_003836.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLK1 | ENST00000341267.9 | c.194A>G | p.His65Arg | missense_variant | Exon 3 of 5 | 1 | NM_003836.7 | ENSP00000340292.4 | ||
DLK1 | ENST00000331224.10 | c.194A>G | p.His65Arg | missense_variant | Exon 3 of 6 | 1 | ENSP00000331081.6 | |||
DLK1 | ENST00000556051.1 | c.194A>G | p.His65Arg | missense_variant | Exon 3 of 3 | 2 | ENSP00000450821.1 | |||
DLK1 | ENST00000392848.9 | c.194A>G | p.His65Arg | missense_variant | Exon 5 of 6 | 4 | ENSP00000376589.5 |
Frequencies
GnomAD3 genomes AF: 0.000513 AC: 78AN: 151904Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000477 AC: 120AN: 251434Hom.: 0 AF XY: 0.000478 AC XY: 65AN XY: 135900
GnomAD4 exome AF: 0.000943 AC: 1378AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.000924 AC XY: 672AN XY: 727230
GnomAD4 genome AF: 0.000513 AC: 78AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42AN XY: 74322
ClinVar
Submissions by phenotype
Silver-Russell syndrome 1 Uncertain:1
The p.(His65Arg) has been identified in the heterozygous state in a patient with a clinical suspicion of Silver Russell syndrome. ). His65 is located within the second EGF-like motif of the extracellular domain of DLK1. This variant was inherited from her healthy mother, who carried the same heterozygous variant. As DLK1 is a maternally imprinted/paternally expressed gene, this variant is unlikely to explain the phenotype of the patient -
not provided Benign:1
DLK1: BS1, BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at