8-144517750-TGCAGCCGCTCCCGCACGTCCC-TGCAGCCGCTCCCGCACGTCCCGCAGCCGCTCCCGCACGTCCC

Variant names:

• chr8-144517750-T-TGCAGCCGCTCCCGCACGTCCC
• rs1445577376
• NM_004260.4:c.14_34dupGGGACGTGCGGGAGCGGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_004260.4(RECQL4):​c.14_34dupGGGACGTGCGGGAGCGGCTGC​(p.Arg5_Leu11dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,328,334 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: RECQL4 NM_004260.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.356
• Publications: 0 publications found

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

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

• PM4: Nonframeshift variant in NON repetitive region in NM_004260.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. 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
	RECQL4	NM_004260.4	MANE Select	c.14_34dupGGGACGTGCGGGAGCGGCTGC	p.Arg5_Leu11dup	conservative_inframe_insertion	Exon 1 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.14_34dupGGGACGTGCGGGAGCGGCTGC	p.Arg5_Leu11dup	conservative_inframe_insertion	Exon 1 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.14_34dupGGGACGTGCGGGAGCGGCTGC	p.Arg5_Leu11dup	conservative_inframe_insertion	Exon 1 of 21	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.14_34dupGGGACGTGCGGGAGCGGCTGC	p.Arg5_Leu11dup	conservative_inframe_insertion	Exon 1 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.-1123_-1103dupGGGACGTGCGGGAGCGGCTGC		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.14_34dupGGGACGTGCGGGAGCGGCTGC	p.Arg5_Leu11dup	conservative_inframe_insertion	Exon 1 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150744 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000153 AC: 18 AN: 1177590 Hom.: 0 Cov.: 32 AF XY: 0.0000157 AC XY: 9 AN XY: 574190

African (AFR) AF: 0.00 AC: 0 AN: 23490

American (AMR) AF: 0.00 AC: 0 AN: 16016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17876

East Asian (EAS) AF: 0.0000399 AC: 1 AN: 25034

South Asian (SAS) AF: 0.00 AC: 0 AN: 48296

European-Finnish (FIN) AF: 0.0000374 AC: 1 AN: 26728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3272

European-Non Finnish (NFE) AF: 0.0000155 AC: 15 AN: 969798

Other (OTH) AF: 0.0000212 AC: 1 AN: 47080

GnomAD4 genome AF: 0.0000332 AC: 5 AN: 150744 Hom.: 0 Cov.: 34 AF XY: 0.0000544 AC XY: 4 AN XY: 73574

African (AFR) AF: 0.0000727 AC: 3 AN: 41238

American (AMR) AF: 0.00 AC: 0 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67540

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.36
Mutation Taster		=79/21	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1445577376; hg19: chr8-145743134;