HNRNPDL p.Leu27Leu

Variant names:

• chr4-82429609-A-A
• NM_031372.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-82429610--
• chr4-82429610-G-A
• chr4-82429610-G-T
• chr4-82429610-G-C
• chr4-82429610-GAG-TAA
• chr4-82429610-GAG-CAA

Variant summary

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

The NM_031372.4(HNRNPDL):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPDL NM_031372.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 0 publications found

Genes affected

HNRNPDL (HGNC:5037): (heterogeneous nuclear ribonucleoprotein D like) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two RRM domains that bind to RNAs. Three alternatively spliced transcript variants have been described for this gene. One of the variants is probably not translated because the transcript is a candidate for nonsense-mediated mRNA decay. The protein isoforms encoded by this gene are similar to its family member HNRPD. [provided by RefSeq, May 2011]

HNRNPDL Gene-Disease associations (from GenCC):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1G

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031372.4. 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
	HNRNPDL	NM_031372.4	MANE Select	c.		exon_region	Exon 1 of 8	NP_112740.1	O14979-1
	HNRNPDL	NM_001207000.1		c.		exon_region	Exon 1 of 7	NP_001193929.1	A0A087WUK2
	HNRNPDL	NR_003249.2		n.		exon_region	Exon 1 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPDL	ENST00000295470.10	TSL:1 MANE Select	c.		exon_region	Exon 1 of 8	ENSP00000295470.5	O14979-1
	HNRNPDL	ENST00000621267.4	TSL:1	c.		exon_region	Exon 1 of 8	ENSP00000483254.1	O14979-1
	HNRNPDL	ENST00000614627.4	TSL:1	c.		exon_region	Exon 1 of 7	ENSP00000478723.1	A0A087WUK2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-83350762;